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Sclerostin and Periostin associated with vascular risk scales in type 2 diabetes

Exciting research news! The BIOMEDICA bioactive Sclerostin and Periostin ELISA kits were used in a groundbreaking study evaluating the association of these bone proteins related to cardiovascular disease (CVD), with the main vascular risk scales in patients with type 2 diabetes.

All Biomedica ELISA assays are fully validated following international quality guidelines.

Bioactive Sclerostin ELISA (cat. no. BI-20472)

• CHARACTERIZED ANTIBODIES – targeting the receptor binding region
• LOW sample volume – 20µl sample /well 

 

Sclerostin ELISA (cat. no. BI-20492)

• TRUSTED – most referenced Sclerostin ELISA (+280 citations)
• LOW sample volume – 20µl sample /well

 

Periostin ELISA (cat. no. BI-20433)

• LOW sample volume – 20µl sample /well
• SPECIFIC – Characterized, epitope mapped capture and detection antibodies:

Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier, E et al.

 

Sclerostin and Periostin associated with vascular risk scales in type 2 diabetes

Type 2 diabetes is linked to an elevated risk of cardiovascular disease (CVD), affecting approximately 35% of patients with the condition (1). As a result, assessing cardiovascular risk is essential for effective disease management in individuals with type 2 diabetes. Various risk scores have been developed to estimate CVD in the general population, including the Framingham Risk Score (FRS), the REGICOR and more recently, the SCORE2-Diabetes was introduced, specifically tailored for individuals with type 2 diabetes (2).

While these computational tools are utilized in clinical practice, there remains a need to investigate new biomarkers that could enhance cardiovascular risk stratification for patients with type 2 diabetes.

Typical bone proteins, including Sclerostin and Periostin, have been linked to cardiovascular disease (CVD). Concurrently, various risk scores have been created to forecast CVD in the general population. The objective of the following study was to examine the relationship between these bone proteins connected to CVD and key vascular risk scales:

Bone proteins are associated with cardiovascular risk according to the SCORE2-Diabetes algorithm. González-Salvatierra S et al., Cardiovasc Diabetol. 2024.  

Key findings:

• Sclerostin and Periostin are associated with vascular risk in the SCORE2-Diabetes algorithm.
• This suggests that Sclerostin and Periostin may serve as useful diagnostic biomarkers for vascular risk in patients with type 2 diabetes.
• Future prospective studies are needed to validate the significance of these bone proteins in assessing vascular risk in the diabetic population.

 

Abstract

Background: Typical bone proteins, such as sclerostin and periostin, have been associated with cardiovascular disease (CVD). Simultaneously, several risk scores have been developed to predict CVD in the general population. Therefore, we aimed to evaluate the association of these bone proteins related to CVD, with the main vascular risk scales: Framingham Risk Score (FRS), REGICOR and SCORE2-Diabetes, in patients with type 2 diabetes. We focus in particular on the SCORE2-Diabetes algorithm, which predicts 10-year CVD risk and is specific to the study population.

Methods: This was a cross-sectional study including 104 patients with type 2 diabetes (62 ± 6 years, 60% males). Clinical data, biochemical measurements, and serum bioactive sclerostin and periostin levels were collected, and different risk scales were calculated. The association between bioactive sclerostin or periostin with the risk scales was analyzed.

Results: A positive correlation was observed between circulating levels of bioactive sclerostin (p < 0.001) and periostin (p < 0.001) with SCORE2-Diabetes values. However, no correlation was found with FRS or REGICOR scales. Both serum bioactive sclerostin and periostin levels were significantly elevated in patients at high-very high risk of CVD (score ≥ 10%) than in the low-moderate risk group (score < 10%) (p < 0.001 for both). Moreover, analyzing these proteins to identify patients with type 2 diabetes at high-very high vascular risk using ROC curves, we observed significant AUC values for bioactive sclerostin (AUC = 0.696; p = 0.001), periostin (AUC = 0.749; p < 0.001), and the model combining both (AUC = 0.795; p < 0.001). For diagnosing high-very high vascular risk, serum bioactive sclerostin levels > 131 pmol/L showed 51.6% sensitivity and 78.6% specificity. Similarly, serum periostin levels > 1144 pmol/L had 64.5% sensitivity and 76.2% specificity.

Conclusions: Sclerostin and periostin are associated with vascular risk in the SCORE2-Diabetes algorithm, opening a new line of investigation to identify novel biomarkers of cardiovascular risk in the type 2 diabetes population.

 

Literature

1. Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management. Ma CX, Ma XN, Guan CH, Li YD, Mauricio D, Fu SB. Cardiovasc Diabetol. 2022 May 14;21(1):74. doi: 10.1186/s12933-022-01516-6. PMID: 35568946.
2. Bone proteins are associated with cardiovascular risk according to the SCORE2-Diabetes algorithm. González-Salvatierra S, García-Martín A, García-Fontana B, Martínez-Heredia L, García-Fontana C, Muñoz-Torres M. Cardiovasc Diabetol. 2024 Aug 24;23(1):311. doi: 10.1186/s12933-024-02406-9. PMID: 39182106.

 

 

Periostin is a soluble extracellular matrix protein that plays a role in bone formation and has been linked to the development of various cancers, including breast cancer. It is secreted in the tumor environment mostly by cancer associated fibroblasts promoting the progression of cancer which includes cell survival, metastasis and also chemoresistance.

Periostin – a prognostic biomarker in breast cancer

The prognostic value of serum Periostin was investigated in a cohort of 509 non metastatic breast cancer patients. The results demonstrated the importance of Periostin in breast cancer and showed that serum Periostin is a prospective indicator for disease prognosis, regardless of the existence of micrometastases. Read more: High serum levels of periostin are associated with a poor survival in breast cancer.

Human serum Periostin levels were measured with the BIOMEDICA PERIOSTIN  ELISA.

Periostin ELISA (cat. no. BI-20433)

• • Low sample volume – 10 µl sample / well
  • For human serum/plasma/cell culture supernatants
  • High quality assay – validation following international guidelines
  • All reagents included – 7 ready to use calibrators and 2 controls
  • Numerous citations using the Biomedica Periostin ELISA

 

example of a BIOMEDICA ELISA assay kit with color-coded reagents, ready to use pre-diluted calibrators/standards and 2 (high/low) kit controls

 

The full characterization of the Periostin ELISA assay has been published in:

Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier E et al., .J Clin Lab Anal. 2018, 32(2):e22252. doi: 10.1002/jcla.22252. 

Also available: Mouse Periostin ELISA (cat. no. BI-20433MS)

• Low sample volume – ≤ 5 µl / well
• For serum/plasma/cell culture supernatants

 

All ELISA kits are developed and manufactured by BIOMEDICA-Vienna/Austria

Related publications

High serum levels of periostin are associated with a poor survival in breast cancer. Rachner TD, Göbel A, Hoffmann O, Erdmann K, Kasimir-Bauer S, Breining D, Kimmig R, Hofbauer LC, Bittner AK. Breast Cancer Res Treat. 2020 Apr;180(2):515-524. doi: 10.1007/s10549-020-05570-0. Epub 2020 Feb 10. PMID: 32040688.

Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways. Labrèche C, Cook DP, Abou-Hamad J, Pascoal J, Pryce BR, Al-Zahrani KN, Sabourin LA. Breast Cancer Res. 2021 Nov 22;23(1):107. doi: 10.1186/s13058-021-01487-8. PMID: 34809697; PMCID: PMC8607680.

Periostin Exon-21 Antibody Neutralization of Triple-Negative Breast Cancer Cell-Derived Periostin Regulates Tumor-Associated Macrophage Polarization and Angiogenesis. Fujikawa T, Sanada F, Taniyama Y, Shibata K, Katsuragi N, Koibuchi N, Akazawa K, Kanemoto Y, Kuroyanagi H, Shimazu K, Rakugi H, Morishita R.Cancers (Basel). 2021 Oct 11;13(20):5072. doi: 10.3390/cancers13205072. PMID: 34680221; PMCID: PMC8533925.

The Role of Extracellular Matrix Proteins in Breast Cancer. Lepucki A, Orlińska K, Mielczarek-Palacz A, Kabut J, Olczyk P, Komosińska-Vassev K. J Clin Med. 2022 Feb 25;11(5):1250. doi: 10.3390/jcm11051250. PMID: 35268340; PMCID: PMC8911242.

Biomedica´s Periostin ELISA kit has recently been featured in a clinical study for lung cancer: Serum Periostin Predicts Survival in Lung Cancer Patients.

Lung adenocarcinoma is the most common type of lung cancer. When first diagnosed, between 30-50% of patients have bone metastasis with poor survival outcome. The extracellular matrix protein Periostin mediates the spreading of lung cancer. In vivo data suggest that bone metastatic lung cancer cells induce Periostin expression that may enhance cancer aggressivity. A recent report in patients with lung adenocarcinoma demonstrates that serum Periostin levels may be used as a prognostic biomarker to predict survival in lung cancer.

Serum Periostin Predicts Survival in Lung Cancer Patients

Learn more: Serum total periostin is an independent marker of overall survival in bone metastases of lung adenocarcinoma. Link to full text.
Massy E, Rousseau JC, Gueye M, Bonnelye E, Brevet M, Chambard L, Duruisseaux M, Borel O, Roger C, Guelminger R, Pialat JB, Gineyts E, Bouazza L, Millet M, Maury JM, Clézardin P, Girard N, Confavreux CB. J Bone Oncol. 2021. 29:100364. doi: 10.1016/j.jbo.2021.100364. PMID: 34150488; PMCID: PMC8190464.

Check out the Biomedica PERIOSTIN ELISA (cat.no. BI-20433)

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Also available: Mouse Periostin ELISA (cat.no. BI-20433MS)

Serum total periostin is an independent marker of overall survival in bone metastases of lung adenocarcinoma

Abstract

More than 35% of lung adenocarcinoma patients have bone metastases at diagnosis and have a poor survival. Periostin, a carboxylated matrix protein, mediates lung cancer cell dissemination by promoting epithelial-mesenchymal transition, and is involved in bone response to mechanical stress and bone formation regulation. This suggests that periostin may be used as a biomarker to predict survival in lung cancer patients. Serum periostin was assessed at diagnosis in a prospective cohort of 133 patients with lung adenocarcinoma of all stages. Patients were divided into localized and bone metastatic groups. Both groups were matched to healthy controls. Survival analysis and Cox proportional hazards models were conducted in the total population and in bone metastatic group. The median serum periostin level was higher in bone metastatic (n = 67; median: 1752 pmol/L) than in the localized group (n = 66; 861 pmol/L; p < 0.0001). Patients with high periostin (>median) had a poorer overall survival in the whole population (33.3 weeks vs. NR; p < 0.0001) and the bone metastatic group (24.4 vs. 66.1 weeks; p < 0.001). In multivariate analysis, patients with high periostin had increased risk of death (HR = 2.09, 95%CI [1.06-4.13]; p = 0.03). This was also found in the bone metastatic group (HR = 3.62, 95%CI [1.74-7.52]; p = 0.0005). Immunohistochemistry on bone metastasis biopsies showed periostin expression in the bone matrix and nuclear and cytoplasmic staining in cancer cells. Serum periostin was an independent survival biomarker in all-stage and in bone metastatic lung adenocarcinoma patients. IHC data suggest that periostin might be induced in cancer cells in bone metastatic niche in addition to bone microenvironment expression.

Related publications

High serum levels of periostin are associated with a poor survival in breast cancer. Link to full text.
Rachner TD, Göbel A, Hoffmann O, Erdmann K, Kasimir-Bauer S, Breining D, Kimmig R, Hofbauer LC, Bittner AK.Breast Cancer Res Treat. 2020 Apr;180(2):515-524. doi: 10.1007/s10549-020-05570-0. Epub 2020 Feb 10.PMID: 32040688.

Abstract
Purpose: Periostin is a secreted extracellular matrix protein, which was originally described in osteoblasts. It supports osteoblastic differentiation and bone formation and has been implicated in the pathogenesis of several human malignancies, including breast cancer. However, little is known about the prognostic value of serum periostin levels in breast cancer. Methods: In this study, we analyzed serum levels of periostin in a cohort of 509 primary, non-metastatic breast cancer patients. Disseminated tumor cell (DTC) status was determined using bone marrow aspirates obtained from the anterior iliac crests. Periostin levels were stratified according to several clinical parameters and Pearson correlation analyses were performed. Kaplan-Meier survival curves were assessed by using the log-rank (Mantel-Cox) test. To identify prognostic factors, multivariate Cox regression analyses were used. Results: Mean serum levels of periostin were 505 ± 179 pmol/l. In older patients (> 60 years), periostin serum levels were significantly increased compared to younger patients (540 ± 184 pmol/l vs. 469 ± 167 pmol/l; p < 0.0001) and age was positively correlated with periostin expression (p < 0.0001). When stratifying the cohort according to periostin serum concentrations, the overall and breast cancer-specific mortality were significantly higher in those patients with high serum periostin (above median) compared to those with low periostin during a mean follow-up of 8.5 years (17.7% vs. 11.4% breast cancer-specific death; p = 0.03; hazard ratio 1.65). Periostin was confirmed to be an independent prognostic marker for breast cancer-specific survival (p = 0.017; hazard ratio 1.79). No significant differences in serum periostin were observed when stratifying the patients according to their DTC status. Conclusions: Our findings emphasize the relevance of periostin in breast cancer and reveal serum periostin as a potential marker for disease prediction, independent on the presence of micrometastases.

Overexpression of periostin predicts poor prognosis in non-small cell lung cancer. Link to full text.
Hong LZ, Wei XW, Chen JF, Shi Y.Oncol. Lett. 2013. 6:1595-1603. doi: 10.3892/ol.2013.1590. Epub 2013 Sep 18.PMID: 24273600.

Abstract
The periostin protein, encoded by the POSTN gene, is a component of the extracellular matrix, which is expressed by fibroblasts and has been observed in a variety of human malignancies. The present study aimed to detect the expression of periostin in the tissues of non-small cell lung cancer (NSCLC) patients and benign lung tumors, and to correlate the results with the clinicopathological data of the subjects, in order to evaluate periostin as a potential prognostic marker. In total, 49 NSCLC patients and 6 benign lung tumors were included in this study. The protein level of periostin was detected in paired normal/paratumor/cancer tissues by a western blot analysis and the mRNA level in paired normal/cancer tissues was detected by quantitative polymerase chain reaction (qPCR). The results were then correlated with established biological and prognostic factors. Immunohistochemistry was used to confirm the location of periostin in the NSCLC tissues. Uni- and multivariate analyses were performed using Cox’s proportional hazards regression model. The protein level of periostin was elevated in the cancer tissue of the NSCLC patients compared with the normal (P=0.017) and paratumor (P=0.000) tissues. The expression level in the male patients was much higher than in the female patients at the protein (P=0.001) and mRNA (P=0.010) levels. The mRNA level in the non-adenocarcinoma (non-ADC) patients was much higher than in the adenocarcinoma (ADC) patients (P=0.029). Periostin was demonstrated higher expression at the protein level in the pseudotumors and tuberculosis patients than in the adjacent (P=0.016) and surrounding tissues (P=0.001). Immunostaining indicated that high levels of periostin were present in the mesenchymal areas, but not in the cancer cells themselves. The patients with tumors exhibiting high-level periostin expression showed a significantly shorter survival time (P=0.036, log-rank test). The 3-year survival rate was 81.5% for patients with low-level periostin expression (periostin-L; n=27) and 45.4% for patients with high-level periostin expression (periostin-H; n=22). Similarly, pathological node (pN) status was a significant prognostic marker in the univariate Cox survival analysis. Notably, periostin-H expression was also identified as an independent prognostic factor by the multivariate analysis (P=0.011). These results showed that the overexpression of periostin predicts a poor prognosis, therefore it may be regarded as a novel molecule in the progression and development of NSCLC. The results provide an additional target for the adjuvant treatment of NSCLC.

Predictive and prognostic value of serum periostin in advanced non-small cell lung cancer patients receiving chemotherapy. Zhang Y, Yuan D, Yao Y, Sun W, Shi Y, Su X. Tumour Biol. 2017. 39(5):1010428317698367. doi: 10.1177/1010428317698367. PMID: 28459197. Full text link.

Mutational profiling of bone metastases from lung adenocarcinoma: results of a prospective study (POUMOS-TEC). Confavreux CB, Girard N, Pialat JB, Bringuier PP, Devouassoux-Shisheboran M, Rousseau JC, Isaac S, Thivolet-Bejui F, Clezardin P, Brevet M. Bonekey Rep. 2014. 3:580. doi: 10.1038/bonekey.2014.75. PMID: 25328676; PMCID: PMC4181073. Full text link.

Diagnostic and prognostic value of serum periostin in patients with non-small cell lung cancer. Xu CH, Wang W, Lin Y, Qian LH, Zhang XW, Wang QB, Yu LK. Oncotarget. 2017. 8(12):18746-18753. doi: 10.18632/oncotarget.13004. PMID: 27816968; PMCID: PMC5386644. Full text link.

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Leucine-rich alpha-2-glycoprotein (LRG) ELISA kit – BI-LRG1 –  Product link

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Leucine-rich α-2-glycoprotein promotes TGFβ1-mediated growth suppression in the Lewis lung carcinoma cell lines. Oncotarget. Takemoto N, Serada S, Fujimoto M, Honda H, Ohkawara T, Takahashi T, Nomura S, Inohara H, Naka T. 2015. 10;6(13):11009-22. doi: 10.18632/oncotarget.3557. PMID: 25826092; PMCID: PMC4484435. Full text link.

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Blood and urine biomarkers are tools to detect diseases, discover drugs and monitor patients. Biomarker research has identified Endostatin and Vanin-1 as promising novel markers to detect microvascular tissue injuries and renal tubular damage in drug-induced acute kidney injury, respectively. These and other proteins e.g. FGF23 and Periostin can easily be detected by ELISA. Check out our assay portfolio for clinical and preclinical research – novel biomarkers in clinical nephrology: www.bmgrp.com.

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 Biomarkers in Clinical Nephrology – FGF23 ∙ Endostatin ∙ Periostin ∙ Vanin-1

ELISA kits developed and manufactured by BIOMEDICA

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Related Publications:

ENDOSTATIN  FOR THE DETECTION OF ADVANCED MICROVASCULAR KIDNEY DAMAGE AND THE PROGRESSION OF KIDNEY DISEASE

Plasma endostatin predicts kidney outcomes in patients with type 2 diabetes. Chauhan K et al.,  Kidney Int,  2019; 95(2):439-446. Link. “Plasma endostatin was strongly associated with kidney outcomes in type 2 diabetics with preserved eGFR and improved risk discrimination over traditional predictors.”

The association between endostatin and kidney disease and mortality in patients with type 2 diabetes. Carlsson et al., Diabetes Metab, 2016; 42(5):351-357. Link. “In patients with T2D, circulating endostatin levels can predict the progression of kidney disease and mortality independently of established kidney disease markers.”

Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival.  Kanbay et al., Eur J Intern Med, 2016; 33:81-87. Link. “Endostatin levels are independently associated with incident CVE in CKD patients.”

Elevated plasma levels of endostatin are associated with chronic kidney disease. Chen et al., Am J Nephrol, 2012; 35(4):335-340. Link. “These data indicate that elevated plasma endostatin is strongly and independently associated with CKD.”

VANIN-1   A MARKER FOR DRUG-INDUCED & SPONTANEOUS ACUTE KIDNEY INJURY AND OBSTRUCTIVE & DIABETIC NEPHROPATHY

Urinary vanin-1 associated with chronic kidney disease in hypertensive patients: A pilot study. Hosohata K et al.,  J Clin Hypertens (Greenwich). 2020 Aug;22(8):1458-1465. Link. “ .. urinary vanin-1 is associated with lower eGFR and higher UPCR and UACR, and might be a potential marker of decreased kidney function in hypertensive patients.”  

A Novel Biomarker for Acute Kidney Injury, Vanin-1, for Obstructive Nephropathy: A Prospective Cohort Pilot Study. Washino et al., Int J Mol Sci, 2019; 20(4).  Link. “Urinary Vanin-1 is a useful biomarker to detect and monitor the clinical course of obstructive nephropathy.”

Urinary Vanin-1 as a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury. Hosohata et al., J Pharm Exp Ther, 2002; 341(3):656–662. Link. “… compared with urinary Kim-1 and NGAL, urinary vanin-1 is an earlier and equally sensitive biomarker for drug-induced AKI.”

Vanin-1: A Potential Biomarker for Nephrotoxicant-Induced Renal Injury. Hosohata et al., Toxicology, 2011; 290(1):82–88.  Link. “These results suggest that vanin-1 is a useful and rapid biomarker for renal tubular injury induced by organic solvents.”

Early Detection of Renal Injury Using Urinary Vanin-1 in Rats with Experimental Colitis. Hosohata et al., J App Tox, 2014; 34(2):184–190. Link. “Compared with Kim-1 and MCP-1, vanin-1 might be an earlier biomarker for the detection of renal injury in rats with experimental colitis.”

Proteomic identification of vanin-1 as a marker of kidney damage in a rat model of type 1 diabetic nephropathy. Fugmann T et al.,  Kidney Int. 2011: ;80(3):272-81. Link

FGF23  FOR RISK PREDICTION IN CHRONIC RENAL INSUFFICIENCY AND TO DETERMINE CARDIOVASCULAR RISK IN CKD

Association of Fibroblast Growth Factor 23 with Atrial Fibrillation in Chronic Kidney Disease, From the Chronic Renal Insufficiency Cohort Study. Mehta et al., JAMA Cardiology, 2016; 1(5):548-556. Link . “Elevated FGF23 is independently associated with prevalent and incident atrial fibrillation in patients with mild to severe CKD.”

Fibroblast growth factor 23 in patients with acute dyspnea: Data from the Akershus Cardiac Examination (ACE) 2 Study.  Lyngbakkena et al., Clin Biochem, 2018; 52:41-47 . Link. “Circulating FGF23 concentrations provide incremental prognostic information to established risk indices in patients with acute dyspnea.”

FGF23 and vitamin D metabolism in chronic kidney disease – mineral bone disorder.  Piec et al., Bone Abstracts, 2016; 5:P469. Link. “cFGF23 is raised in patients with CKD as a compensatory response to hyperphosphatemia or phosphate overload.”

Renal and Extrarenal Effects of Fibroblast Growth Factor 23. Vervloet, Nature Reviews, 2019; Nephrology 1(2):109–120. Link. “.. FGF23 is also a valuable biomarker as it predicts risk of a wide variety of clinical events, in particular heart failure.”

PERIOSTIN   A BIOMARKER FOR SEVERITY, PROGRESSION AND RESPONSE TO THERAPY IN HUMAN KIDNEY DISEASE ASSOCIATED TO HYPERTENSION

Identification of periostin as a critical marker of progression/reversal of hypertensive nephropathy. Guerrot et al., PLoS One, 2012; 7(3):e31974. Link.  “… the results identify Periostin as a previously unrecognized marker associated with hypertensive nephropathy.”

Periostin Induces Kidney Fibrosis after Acute Kidney Injury via the p38 MAPK Pathway. An et al., Am J Physiol Renal Physiol, 2019; 316(3):F426-F437. Link. “Periostin promotes kidney fibrosis via the p38 MAPK pathway following acute kidney injury triggered by a hypoxic or ischemic insult. Periostin ablation may protect against chronic kidney disease progression”.

Periostin as a tissue and urinary biomarker of renal injury in type 2 diabetes mellitus. Satirapoj et al., PLoS One, 2015; 17; 10(4):e0124055. Link.  “Urinary periostin is an associated renal derangement in patients with established diabetic nephropathy and it may be used as an early marker of diabetic renal injury.” 

Urinary Periostin Excretion Predicts Renal Outcome in IgA Nephropathy. Hwang et al., Am J Nephrol, 2016; 44(6):481-492. Link.  “POSTN/Cr value at initial diagnosis correlated with renal fibrosis and predicted the renal outcomes in patients with IgAN. It could be a promising urinary biomarker for renal fibrosis.”

Effects of periostin deficiency on kidney aging and lipid metabolism. An JN Aging (Albany NY). 2021. 13(19):22649-22665. Link.

Periostin in the Kidney. Wallace DP. Adv Exp Med Biol. 2019;1132:99-112. Link.

The research status and prospect of Periostin in chronic kidney disease. Jia YY, Yu Y, Li HJ. Ren Fail. 2020 Nov;42(1):1166-1172. Link.

Polycystic Kidney Disease and Renal Fibrosis. Xue C, Mei CL. Adv Exp Med Biol. 2019;1165:81-100. Link.

Periostin Promotes Cell Proliferation and Macrophage Polarization to Drive Repair after AKI. Kormann R J Am Soc Nephrol. 2020; 31(1):85-100. Link.

Kidney Injury Molecule-1 and Periostin Urinary Excretion and Tissue Expression Levels and Association with Glomerular Disease Outcomes. Wu Q Glomerular Dis. 2021 Jun;1(2):45-59. doi: 10.1159/000513166. Epub 2021. Link.

SCLEROSTIN  FOR THE DIAGNOSIS OF HIGH BONE TURNOVER IN CKD AND THE PREDICTION OF CORONARY ARTERY CALCIFICATION

Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD.  Behets et al., PLOS ONE, 2017; 12(5). Link.  “Sclerostin, as opposed to DKK1, may qualify as a biomarker of CKD-MBD, particularly in dialysis patients.”

Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Cejka et al., Nephrol Dial Transplant, 2012; 27:226-230.  Link. “Dialysis patients had significantly higher Sclerostin levels than controls.”

Serum Sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients.  Kanbay et al., J Clin Endocrinol, 2014; 99(10):E1854–E1861. Link. “Serum sclerostin values are associated, even after multiple adjustments, with fatal and nonfatal cardiovascular events in a nondialyzed CKD population.”

Relationship between plasma levels of sclerostin, calcium–phosphate disturbances, established markers of bone turnover, and inflammation in haemodialysis patients. Pietrzyk et al., Int Urol Nephrol, 2019; 51(3):519-526. Link. “Increased circulating sclerostin levels seem to reflect slower bone turnover in HD patients. Low levels of sclerostin are associated with vitamin D deficiency and good phosphates alignment.”

Sclerostin in chronic kidney disease-mineral bone disorder think first before you block it! Brandenburg VM et al.,  Nephrol Dial Transplant,  2019; ;34(3):408-414. Link

Breast cancer is the most common cancer in women worldwide. Improving our understanding of how breast cancer originates, grows and spreads may help to reduce the risk and burden of the disease.

Periostin and NRP1 –  markers for breast cancer survival

Biomarker research, has identified the novel protein markers Periostin and Neuropilin-1 as promising  prognostic markers for breast cancer-specific survival. These proteins can easily be detected in human serum and plasma by ELISA assay.

Periostin and NRP1 – prognostic markers for breast cancer survival

Periostin (POSTN) and Neuropilin-1 (NRP1) ELISA kits

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PROGNOSTIC MARKERS FOR BREAST CANCER SURVIVAL

Publications on Periostin and Neuropilin-1 applied in breast cancer research:

High serum levels of periostin are associated with a poor survival in breast cancer.  Rachner TD et al., 2020,  link.

 Abstract:

Purpose: Periostin is a secreted extracellular matrix protein, which was originally described in osteoblasts. It supports osteoblastic differentiation and bone formation and has been implicated in the pathogenesis of several human malignancies, including breast cancer. However, little is known about the prognostic value of serum periostin levels in breast cancer.

Methods: In this study, we analyzed serum levels of periostin in a cohort of 509 primary, non-metastatic breast cancer patients. Disseminated tumor cell (DTC) status was determined using bone marrow aspirates obtained from the anterior iliac crests. Periostin levels were stratified according to several clinical parameters and Pearson correlation analyses were performed. Kaplan-Meier survival curves were assessed by using the log-rank (Mantel-Cox) test. To identify prognostic factors, multivariate Cox regression analyses were used.

Results: Mean serum levels of periostin were 505 ± 179 pmol/l. In older patients (> 60 years), periostin serum levels were significantly increased compared to younger patients (540 ± 184 pmol/l vs. 469 ± 167 pmol/l; p < 0.0001) and age was positively correlated with periostin expression (p < 0.0001). When stratifying the cohort according to periostin serum concentrations, the overall and breast cancer-specific mortality were significantly higher in those patients with high serum periostin (above median) compared to those with low periostin during a mean follow-up of 8.5 years (17.7% vs. 11.4% breast cancer-specific death; p = 0.03; hazard ratio 1.65). Periostin was confirmed to be an independent prognostic marker for breast cancer-specific survival (p = 0.017; hazard ratio 1.79). No significant differences in serum periostin were observed when stratifying the patients according to their DTC status.

Conclusions: Our findings emphasize the relevance of periostin in breast cancer and reveal serum periostin as a potential marker for disease prediction, independent on the presence of micrometastases.

 

Development of an engineered peptide antagonist against periostin to overcome doxorubicin resistance in breast cancer. Oo KK et al., 2021, link.

 

Abstract:

Background: Chemoresistance is one of the main problems in treatment of cancer. Periostin (PN) is a stromal protein which is mostly secreted from cancer associated fibroblasts in the tumor microenvironment and can promote cancer progression including cell survival, metastasis, and chemoresistance. The main objective of this study was to develop an anti-PN peptide from the bacteriophage library to overcome PN effects in breast cancer (BCA) cells.

Methods: A twelve amino acids bacteriophage display library was used for biopanning against the PN active site. A selected clone was sequenced and analyzed for peptide primary structure. A peptide was synthesized and tested for the binding affinity to PN. PN effects including a proliferation, migration and a drug sensitivity test were performed using PN overexpression BCA cells or PN treatment and inhibited by an anti-PN peptide. An intracellular signaling mechanism of inhibition was studied by western blot analysis. Lastly, PN expressions in BCA patients were analyzed along with clinical data.

Results: The results showed that a candidate anti-PN peptide was synthesized and showed affinity binding to PN. PN could increase proliferation and migration of BCA cells and these effects could be inhibited by an anti-PN peptide. There was significant resistance to doxorubicin in PN-overexpressed BCA cells and this effect could be reversed by an anti-PN peptide in associations with phosphorylation of AKT and expression of survivin. In BCA patients, serum PN showed a correlation with tissue PN expression but there was no significant correlation with clinical data.

Conclusions: This finding supports that anti-PN peptide is expected to be used in the development of peptide therapy to reduce PN-induced chemoresistance in BCA.

 

 Neuropilin-1 is a marker of poor prognosis in early breast cancer. Rachner TD et al., 2021, link.

 

Abstract:

Background: Neuropilin-1 (NRP-1) is a transmembrane protein that acts as a multifunctional non-tyrosine kinase receptor with an established role in development and immunity. NRP-1 also regulates tumor biology, and high expression levels of tissue NRP-1 have been associated with a poor prognosis. Recently, ELISA-based quantification of soluble NRP-1 (sNRP-1) has become available, but little is known about the prognostic value of sNRP-1 in malignancies.

Materials and methods: We measured sNRP-1 in the serum of 509 patients with primary early breast cancer (BC) at the time of diagnosis using ELISA.

Results: Mean serum values of sNRP-1 were 1.88 ± 0.52 nmol/l (= 130.83 ± 36.24 ng/ml). SNRP-1 levels weakly correlated with age, and were higher in peri- and postmenopausal patients compared to premenopausal patients, respectively (p < 0.0001). Low levels of sNRP-1 were associated with a significant survival benefit compared to high sNRP-1 levels at baseline (p = 0.005; HR 1.94; 95%CI 1.23-3.06). These findings remained significant after adjustment for tumor stage including lymph node involvement, grading, hormone receptor, HER2 status, and age (p = 0.022; HR 1.78; 95%CI 1.09-2.91).

Conclusion: Our findings warrant further investigations into the prognostic and therapeutic potential of sNRP-1 in BC.

 

Chronic allergic itch is a common symptom affecting millions of people, but its pathogenesis is not fully understood. Periostin is an extracellular matrix protein that is highly expressed in the skin. Researchers have identified that Periostin can directly activate itch-associated neurons in the skin. Blocking the Periostin receptors on these neurons reduced the itch response in a mouse model.

Related publications: Periostin, an Emerging Player in Itch Sensation.
https://lnkd.in/g8dwQ3z
Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch.
https://lnkd.in/gMyJM3X

PERIOSTIN can reliably be measured by ELISA . Only 10 µl of sample volume is required! https://buff.ly/35zhkBz

Biomedica Periostin ELISA – Features & Benefits
√ CONVENIENT – Assay range optimized for clinical samples
√ RELIABLE – Full validation package
√ SPECIFIC – Characterized, epitope mapped capture and detection antibodies
√ HIGH QUALITY GUARANTEED–  https://lnkd.in/gmGhJgR

Periostin functions as a ligand for integrins to support adhesion and migration of tumor cells which leads to increased cell survival, invasion, angiogenesis and metastasis in different cancer types including breast cancer (BC).
In a recent study using the Biomedica Human Periostin ELISA, Periostin levels were significantly increased in women with primary, non-metastatic breast cancer over 60 as well as in postmenopausal women. No difference was observed in patients with and without the presence of disseminated tumor cells. However, high levels of circulating Periostin were associated with a poorer BC specific survival. These results warrant further studies on the role of Periostin in cancer patients.

More information on the Biomedica Periostin assays can be found here.
Hoffman et al. High circulating levels of Periostin are associated with a poor survival in primary, non-metastatic breast cancer patients. Am Ass Cancer Res 2019; 79(4 Suppl):Abstract nr P6-09-08

Spinal cord injury (SCI) induces an acute alteration in bone metabolism. Although the aetiology of the bone disturbances is not precisely known, immobilisation reduces mechanical loading and the morphology of osteocytes, which are the primary mechanosensors. Periostin and Sclerostin are secreted mostly by osteocytes and are involved in bone’s mechanical response.

In a recent study using the Biomedica Periostin ELISA and Sclerostin ELISA, individuals with spinal cord injury presented higher serum Periostin levels in the acute phase and normal values in the chronic phase.

Conversely, serum Sclerostin levels were suppressed whatever the post-injury duration in the individuals with spinal cord injury. Paraplegia vs. tetraplegia and fragility fracture status seemed to influence Sclerostin levels only.

Maïmoun et al. Periostin and Sclerostin levels in individuals with spinal cord injury and their relationship with bone mass, bone turnover, fracture and osteoporosis status. Bone. 2019 127:612-619.

FluoBolt™ Periostin assay highlights:

• 
  High sensitivity
• 
  Single step
• 
  No enzyme substrate required

Human Periostin ELISA highlights:

• 
  Only assay that detects all known Periostin isoforms
• 
  Extensively validated according to FDA/ICH/EMEA guidelines
• 
  7 human serum-based standards and 2 controls included

Chronic kidney disease (CKD) is a major global health concern, affecting roughly 10 percent of the population, totaling more than 850 million people (1, 2).

CKD involves progressive nephron loss, compensatory hyperfiltration in remaining nephrons, and subsequent glomerulosclerosis (3, 4). This process is often driven by etiologies such as diabetic nephropathy (5), glomerulonephritis, and other systemic or intrinsic renal diseases.

Biochemical hallmarks include decreased clearance of nitrogenous waste products such as urea and creatinine, leading to azotemia (6). The disruption of electrolyte homeostasis may result in hyperkalemia, metabolic acidosis, and disturbances in calcium-phosphate balance, contributing to secondary hyperparathyroidism and vascular calcification (7).

CKD progression is associated with increased cardiovascular morbidity and mortality (8).The disease course can be monitored via estimated glomerular filtration rate (eGFR), albuminuria levels, and imaging findings of renal morphology (9).

Role of the Kidneys

Kidneys are vital organs that regulate fluid balance, blood pressure and produce hormones that stimulate the production of red blood cells . Kidney disease is a condition in which kidneys lose their ability to effectively filter waste products and excess fluids from the blood. Kidney disease commonly leads to a decline in kidney function that may lead to kidney failure, characterized by the complete loss of kidney function. At this stage dialysis or kidney transplantation become the only treatment option.

Kidney problems can emerge suddenly (acute) or gradually over time (chronic). Various conditions, diseases and medications can contribute to acute and chronic kidney problems.  Chronic kidney disease (CKD) is characterized by a prolonged period of kidney abnormalities that last for more than three months (10), whereas acute kidney disease – acute kidney injury (AKI) is characterized by a sudden loss of excretory kidney function (11).

Other forms of kidney disease include polycystic kidney disease (PKD) a genetic disorder that leads to kidney enlargement and impaired kidney function over time and glomerulonephritis (GN) (12). GN is a group of diseases characterized by inflammation of the glomeruli, the filtration units of the kidney (13).

Novel Biomarkers in Nephrology

FGF23  •  SCLEROSTIN  •  ENDOSTATIN  •  VANIN-1  •  PERIOSTIN

Advancements in nephrology have led to the identification of several emerging biomarkers that enhance early detection, prognosis, and understanding of kidney injury and disease progression. These novel biomarkers could provide more sensitive and specific insights compared to traditional measures like serum creatinine and albuminuria.

FGF23  – in Acute Kidney Injury

Fibroblast growth factor 23 (FGF23) is a hormone produced by bone that plays a key role in regulating phosphate excretion by the kidneys. In the context of kidney disease, declining renal function leads to an increase in serum phosphate levels, which in turn stimulates the secretion of FGF23. Elevated phosphate levels are also frequently observed in patients with acute kidney injury (AKI) (14).

FGF23 as a Marker of Adverse Outcomes in AKI

Levels of FGF23 rise rapidly during AKI and have been associated with the need for renal replacement therapy (14-17). Furthermore, FGF23 levels possess prognostic value, as demonstrated in a large study  in over 1500 patients with AKI (16).

FGF23 and Sclerostin – Novel Biomarkers in Diabetic Kidney Disease

Growing evidence indicates that FGF23 may be involved in type 2 diabetes (T2DM), as levels of FGF23 are elevated in these patients—even among those with normal kidney function—when compared to the general population (18). A recent study demonstrated phosphate-independent effects of FGF23 following glucose loading, showing associations between FGF23 and levels of glucose, insulin, and proinsulin, as well as obesity (19). Additionally, FGF23 has been linked to the development of gestational diabetes mellitus (20).

Sclerostin is a protein produced by bone cells that inhibits bone formation. Recent research suggests that sclerostin also influences lipid and glucose metabolism, as serum sclerostin levels are negatively associated with insulin sensitivity in obese women, but not in lean women (21). Elevated sclerostin levels have also been observed in individuals with prediabetes (22).

 FGF23 and Sclerostin can reliable by measured with conventional ELISA assays from BIOMEDICA.

• FGF23 (C-terminal) |BI-20700 and FGF23 intact ELISA |BI-20700               
• Sclerostin ELISA |BI-20492 and Bioactive Sclerostin ELISA |BI-20472    

 

Endostatin – A Potential Biomarker for Renal Fibrosis, CKD, and Prognosis in AKI

Endostatin is a protein found in the extracellular matrix that is expressed during the progression of renal fibrosis. Elevated serum levels of endostatin may result from increased degradation of the extracellular matrix in patients with chronic kidney disease (CKD) (23, 24). Additionally, endostatin has been explored as a prognostic marker in individuals with acute kidney injury (AKI) (25) and has been independently linked to the occurrence of cardiovascular events in CKD patients (26).

Endostatin can reliably be quantified in serum, plasma and urine samples:

• Endostatin ELISA | BI-20742

 

VANIN-1 – A Potential Biomarker for Acute Kidney Injury and Drug-Induced Renal Injury

Vascular non-inflammatory molecule-1 (Vanin-1) is highly expressed in the kidney (27) and has been proposed as a biomarker for acute kidney injury (AKI) and drug-induced renal damage (28). It has also been identified as an indicator of kidney injury in a rat model of type 1 diabetic nephropathy (29).

Urinary Vanin-1 has been studied in children with renal fibrosis (30) and as a potential predictor of acute pyelonephritis in young children with urinary tract infections (31). More recently, research has explored the role of urinary Vanin-1 in kidney transplant recipients (32).

Vanin-1 can easily be measured with a conventional ELISA assay:

• Vanin-1 (urine) ELISA | BI-VAN1U  (33)

 

PERIOSTIN – A Potential Early Biomarker of Renal Tubular Injury

Periostin is a matricellular protein involved in tissue remodeling and wound healing processes. Research has shown that Periostin expression in the kidney correlates with the extent of interstitial fibrosis and a decline in renal function (34). Elevated levels of urinary Periostin have been observed in patients with type 2 diabetes, even before the appearance of microalbuminuria. These findings suggest that urinary Periostin may serve as an early marker of renal tubular injury (35).

Periostin can be accurately measured in serum, plasma, and urine through a fully validated ELISA assay (36).

• Periostin ELISA | BI-20422

 

BIOMEDICA – HIGH QUALITY ASSAYS – Fully validated according to international quality guidelines

• TRUSTED – Widely cited in over 1800 publications

 

 

See our brochure on Biomarkers in Clinical Nephrology  

 

Literature

1. ISN- International Society of Nephrology
2. Global Facts: About Kidney Disease
3. Remnant nephron physiology and the progression of chronic kidney disease. Schnaper HW. Pediatr Nephrol. 2014; 29(2):193-202.  PMID: 23715783.
4. Mechanisms of progression of chronic kidney disease. Fogo AB. Pediatr Nephrol. 2007;  22(12):2011-22. PMID: 17647026.
5. Classification and Differential Diagnosis of Diabetic Nephropathy. Qi C et al.,  J Diabetes Res. 2017; 2017:8637138. PMID: 28316995.
6. Azotemia. Tyagi A, Aeddula NR. 2023;  In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 30844172.
7. Understanding Vascular Calcification in Chronic Kidney Disease: Pathogenesis and Therapeutic Implications. Siracusa C et al., Int J Mol Sci. 2024; 25(23):13096. PMID: 39684805.
8. The Dual Burden: Exploring Cardiovascular Complications in Chronic Kidney Disease. Biomolecules. Caturano A et al., 2024: 14(11):1393. PMID: 39595570.
9. The KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD), 2024. Chronic Kidney Disease Diagnosis and Management: A Review. Chen TK, Knicely DH, Grams ME. JAMA. 2019 Oct 1;322(13):1294-1304. doi: 10.1001/jama.2019.14745. PMID: 31573641; PMCID: PMC7015670.
10. Chronic Kidney Disease Diagnosis and Management: A Review. Chen TK et al.,  JAMA. 2019; 322(13):1294-1304.  PMID: 31573641.
11. Acute kidney injury. Kellum JA et al.,. Nat Rev Dis Primers. 2021; 15;7(1):52. PMID: 34267223.  
12.  Treatment of Autosomal-Dominant Polycystic Kidney Disease. Jdiaa SS et al.,. Am J Kidney Dis. 2025; 85(4):491-500.  PMID: 39424253.
13. Advances in primary glomerulonephritis. Ellison B et al.,  J Hosp Med (Lond). 2024; 30;85(7):1-11. PMID: 39078905.
14. Fibroblast Growth Factor 23 and Klotho in AKI. Christov M, Neyra JA, Gupta S, Leaf DE. Semin Nephrol. 2019 Jan;39(1):57-75. doi: 10.1016/j.semnephrol.2018.10.005. PMID: 30606408. 
15. Fibroblast Growth Factor 23 Regulation and Acute Kidney Injury. Zhou W et al.,  Nephron. 2022;146(3):239-242. PMID: 34284404. 
16. Fibroblast growth factor 23 associates with death in critically ill patients. Leaf DE et al., Am Clin J Am Soc Nephrol. 2018. 13(4):531–41. 
17. FGF-23 levels in patients with AKI and risk of adverse outcomes. Leaf DE et al., Clin J Am Soc Nephrol. 2012. 7(8):1217-23. 
18. Earlier onset and greater severity of disordered mineral metabolism in diabetic patients with chronic kidney disease Wahl P et al. 2012.  Diabetes Care 35, 994–1001.  
19. Fibroblast Growth Factor 23, Glucose Homeostasis, and Incident Diabetes: Findings of 2 Cohort Studies, Amarens van der Vaart et al., 2023. The Journal of Clinical Endocrinology & Metabolism,  108, 10,  e971–e978.
20. Fibroblast growth factor 23 is associated with the development of gestational diabetes mellitus. Hocher CF et al., Diabetes Metab Res Rev. 2023. 8:e3704. PMID: 37553983.
21. Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women. Aznou A et al., Endocr Connect. 2021. 10(2):131-138. PMID: 33480863.
22. Sclerostin and Insulin Resistance in Prediabetes: Evidence of a Cross Talk Between Bone and Glucose Metabolism. Daniele G et al., Diabetes Care. 2015. 38(8):1509-17.  PMID: 26084344.
23. A defective angiogenesis in chronic kidney disease. Futrakul N et al., Ren Fail. 2008. 30(2):215-7.  PMID: 18300124.
24. Endostatin in Renal and Cardiovascular Diseases. Li M et al., Kidney Dis (Basel). 2021.9;7(6):468-481. PMID: 34901193.
25. Prognostic value of dynamic plasma endostatin for the prediction of mortality in acute kidney injury: A prospective cohort study. Jia HM et al.,  J Int Med Res. 2020.  48(7):300060520940856. PMID: 32691651.
26. Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival. Kanbay M et al., Eur J Intern Med. 2016. 33:81-7.  PMID: 27394925.
27. Chemical biology tools to study pantetheinases of the vanin family. Schalkwijk, J, Jansen, P. Biochem Soc Trans. 2014. 42, 1052–1055.
28. Urinary Vanin-1 As a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury. Hosohata K et al.J  Pharm  Exp Ther. 2012. 341, 656–662.
29. Proteomic identification of vanin-1 as a marker of kidney damage in a rat model of type 1 diabetic nephropathy. Fugmann T et al., Kidney Int. 2011. 80, 272–281.
30. The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis-A Pilot Study. Mizerska-Wasiak M et al.,  J Clin Med. 2022. 11(5):1265. PMID: 35268356. 
31. Urinary vanin-1 for predicting acute pyelonephritis in young children with urinary tract infection: a pilot study. Krzemień G et al., Biomarkers. 2021. 26(4):318-324.
32. Urinary vanin-1, tubular injury, and graft failure in kidney transplant recipients. Alkaff FF et al., Sci Rep. 2024. 4(1):2283.  PMID: 38280883.
33. Development of an immunoassay that reveals altered uninary Vanin-1 in human with kidney disease. Wallwitz, J.,  et al.,. 2018. Nephrology Dialysis Transplantation, Volume 33, Issue suppl_1, Page i126. 
34. Periostin in the Kidney. Wallace DP et al., Adv Exp Med Biol. 2019, 1132:99-112.
35. Periostin as a tissue and urinary biomarker of renal injury in type 2 diabetes mellitus. Satirapoj B et al., PLoS One. 2015, 17;10(4):e0124055.
36. Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier E et al., J Clin Lab Anal. 2018, 32(2):e22252.

We are excited to be soon attending the ECTS Congress in Innsbruck, Austria from May 23-26, 2025. Meet us at our banner exhibition “Biomedica´s Bone Marker ELISAs” and explore our kits including SCLEROSTIN, OPG, RANKL, FGF23, PERIOSTIN, and many others.

We look forward to connecting with you!

Join us at ECTS 

Click here for more information about the congress.

The ECTS 2025 Congress is recognized as the premier annual gathering in Europe dedicated to this field. The congress offers a comprehensive and engaging scientific program that covers the most recent advances, challenges, and debates related to bone and calcified tissues. The program aims to unite researchers,  clinicians, and health professionals, showcasing their latest research.

Biomarkers in Bone Biology
Bone cells produce biomarkers throughout the process of bone remodeling. These biomarkers are valuable for evaluating bone diseases and serve as potential therapeutic targets. They can be readily identified in serum and plasma samples using immunoassay techniques.

A recent review by Fernández-Villabrille S et al.,  Novel Biomarkers of Bone Metabolism explores some emerging biomarkers in mineral and bone metabolism like:

Receptor Activator of NFkappa B lingand (RANKL), Osteoprotegerin (OPG), Sclerostin (SOST), Dickkopf-1 (DKK-1), Periostin (POSTN) and others.

 

BIOMEDICA offers quality Bone Marker ELISA assay kits: 

-Sclerostin ELISA (SOST; cat.no. BI-20492)  

-OPG ELISA (Osteoprotegerin; cat.no. BI-20403)  

-RANKL ELISA (soluble RANKL; cat.no. BI-20462)  

-DKK-1 ELISA (Dickkopf-1; cat.no. BI-20413)  

-FGF23 intact ELISA (Fibroblast growth factor-23 intact; cat.no. BI-20700) 

-FGF23 C-terminal ELISA  (Fibroblast growth factor-23 C-terminal; cat.no. cat.no. BI-20702) 

-PERIOSTIN ELISA (POSTN, BI-20433) 

-NT-proCNP ELISA (NT-C-type natriuretic peptide, BI-20812)

 

 TRUSTED – cited in over 1300 publications

• Kit validations follows international quality guidelines
• Developed & manufactured by Biomedica in Austria

 

About SCLEROSTIN

Sclerostin (SOST), primarily produced by osteocytes, is regarded as a key regulator of bone formation. It functions as a soluble antagonist of the Wnt signaling pathway. Inhibition of this pathway results in bone resorption, whereas activation of Wnt signaling stimulates bone formation.

About PERIOSTIN

Periostin (POSTN) is an extracellular matrix protein predominantly expressed in the periosteum, the membrane covering the outer surface of bones that plays a role in bone growth. It is involved in various processes, including bone biology, tissue repair, cancer, cardiovascular and respiratory conditions, as well as in numerous inflammatory conditions such as asthma.

Osteoporosis is a bone disease characterized by progressive loss of bone density, leading to an increased risk of fractures, particularly in the hip, spine, and wrist. It occurs when the balance between bone resorption and bone formation is disrupted, often due to factors such as aging, hormonal changes (especially post-menopause in women), nutritional deficiencies (such as calcium and vitamin D), sedentarism, and certain medications or medical conditions (1).

The prevalence of osteoporosis among older adults is significant: it is estimated that over 200 million people suffer from osteoporosis worldwide, with about one in three women and one in five men over the age of 50 experiencing an osteoporotic fracture in their lifetime (1). Osteoporosis represents a major public health concern due to its impact on mobility, quality of life, and healthcare costs associated with fracture management and treatment. Surprisingly, in women over 45 years of age, osteoporosis accounts for more days in hospital than may other diseases, including diabetes, myocardial infarction and breast cancer (3).

Bone Health and Osteoporosis

How can Osteoporosis be prevented ?

Regular exercise and a healthy diet, including the intake of key nutrients like Vitamin D and Calcium, are some key factors that can help in preventing the disease (2).

–Calcium: a healthy adult body contains around 1 kg of calcium, 99% of which is deposited in bone and teeth (4). Good sources of calcium include dairy products, leafy green vegetables, fortified foods, and fish with bones (1).

–Vitamin D: vitamin D plays an important role in regulating calcium and maintaining bone health. Although vitamin D influences various aspects of bone and calcium metabolism, one of its most important functions is the regulation of the efficiency of intestinal calcium (Ca) absorption (5).

The primary source of vitamin D is sunlight; it is synthesized in the skin. The form of vitamin D produced in the skin is known as vitamin D3 (cholecalciferol), while the dietary forms can be either vitamin D3 or a closely related plant-derived compound called vitamin D2 (ergocalciferol). Only a limited number of foods are naturally high in vitamin D. Dietary sources include fatty fish like salmon, sardines, and mackerel, as well as eggs, liver, and in some regions, fortified products such as margarine, dairy items, and cereals. For more information on sources on vitamin D and Vitamin D recommendations : https://www.osteoporosis.foundation/vitamin-d-recommendations.

-Other potentially risk factors for osteoporosis are smoking, alcohol consumption, low or excessive phosphorus intake, protein deficiency or a high-protein diet, excessive consumption of coffee, a sedentary lifestyle or lack of mobility, and insufficient exposure to the sun (6). 

Role of the human skeleton

The human skeleton provides support and structure for the body, protecting vital organs like the brain and heart. It is an important component of the musculoskeletal system, enabling movement. The skeleton also produces blood cells in its bone marrow and stores essential minerals like calcium. The skeleton is  constantly remodeled throughout life, with old bone being broken down and replaced by new tissue to maintain bone mass. This ongoing process of bone resorption and growth is called bone metabolism.

Bone remodeling

Bone remodeling is a continuous and regulated process where various specialized cells primarily osteoclasts breaking down old bone tissue, and osteoblasts building new bone, are involved. These cells constantly interact via factors like osteoprotegerin (OPG) and RANKL (receptor activator of nuclear factor kappa-B ligand) to maintain a healthy balance between bone resorption and bone formation. Imbalances in this process can lead to bone diseases like osteoporosis.  

Bone cells act as endocrine cells, influencing other organs. Osteocytes, the most common bone cell type embedded within the bone, are key regulators of bone formation. They play an important role in bone remodelling and release specific biomarkers such as sclerostin (SOST), fibroblast growth factor 23 (FGF23), and Dickkopf-1 (DKK-1).

 

Biomedica offers a range of ELISA kits to measure bone biomarkers in serum, plasma, and cell cultures

SCLEROSTIN (SOST; cat.no. BI-20492)

OPG  (Osteoprotegerin; cat.no. BI-20403)

RANKL  (soluble RANKL; cat.no. BI-20462)

DKK-1  (Dickkopf-1; cat.no. BI-20413)

FGF23 intact (Fibroblast growth factor-23, intact; cat.no. BI-20700)

FGF23 C-terminal  (Fibroblast growth factor-23, C-terminal; cat.no. cat.no. BI-20702)

PERIOSTIN  (POSTN, BI-20433)

 

• TRUSTED – cited in over 1200 publications
• Kit validations follows international quality guidelines
• Developed & manufactured by Biomedica in Austria

 

Literature

1. Assessment of osteoporosis at the primary health-care level. WHO Scientific Group Technical Report. Kanis J. 2007  [Accessed 22.02.2019];
2. The clinician’s guide to prevention and treatment of osteoporosis. LeBoff M et al. Osteoporos Int 33, 2049–2102 (2022).
3. The prevalence of vertebral deformity in european men and women: the European Vertebral Osteoporosis Study. O’Neill TW et al., J Bone Miner Res, 1996. 11(7): p. 1010-8.
4. Physiology of Calcium Homeostasis: An Overview. Matikainen N et al., Endocrinol Metab Clin North Am. 2021; 50(4):575-590. PMID: 34774235.
5. Vitamin D-Mediated Regulation of Intestinal Calcium Absorption . Fleet JC. Nutrients. 2022 Aug 16;14(16):3351. PMID: 36014856.
6. Osteoporosis – risk factors, pharmaceutical and non-pharmaceutical treatment. Tański W et al., Eur Rev Med Pharmacol Sci. 2021; 25(9):3557-3566. PMID: 34002830.

 

The Enzyme Linked Immunosorbent Assay (ELISA) is a widely used laboratory technique designed to detect and quantify proteins, hormones, antibodies, and other molecules in samples such as serum, plasma, saliva, urine, or cell culture supernatants. ELISA assays are used in various fields, including clinical diagnostics and research.  

Selecting the right ELISA kit is an important decision that greatly impacts the results of your experiments. By thoughtfully evaluating factors like sensitivity, dynamic range, precision, and workflow you can make a well-informed decision that aligns with your research objectives. Other parameters that are better indicators of ELISA performance should also be considered. These include type of samples to be measured, recovery, dilution linearity and parallelism (%) to measure the target protein in real samples like plasma, serum, or cell culture media.

ELISA Assay Principle

The main principle of an ELISA involves the binding of an antigen (the target molecule) to a specific antibody. The assay is mostly carried out in a 96-well plate that is coated with capture antibodies specific to the target antigen.

 

ELISA Assay Protocol- Example:

1. Coating: The wells of the 96-well ELISA microplate are coated with a specific capture antibody that binds to the target antigen.
2. Sample Addition: The sample containing the target antigen is added to the wells. Antigen present in the sample binds to coated capture antibody.
3. Detection Antibody: A secondary antibody that is linked to an enzyme, is then added to the wells. It binds specifically to the target antigen, forming a sandwich complex (capture antibody- antigen – secondary antibody).  
4. Substrate Addition: A substrate (e.g. TMB Tetramethylbenzidine) is added to the wells. The enzyme catalyzed color change of the substrate is directly proportional to the amount of target protein present in the sample.
5. Signal Measurement: The color change and the intensity of the color is directly proportional to the amount of target antigen in the samples. It is detectable with a standard microtiter plate ELISA reader (spectrophotometer). A dose response curve of the absorbance (optical density, e.g. OD at 450 nm) versus the standard concentration is generated, using the values obtained from the standards (calibrators).

 

ELISA Assay, 96 well microtiter plate

 

How to select the right ELISA kitBefore purchasing an ELISA assay, always read the kit protocol booklet (package insert). This may help to decide if the kit will be suitable for your needs.

Check as follows:

1. ANALYTE

Which protein biomarker will you be measuring? Be sure to use the correct term during your search. Some biomarker proteins have alternative names (e.g. PERIOSTIN or POSTN ELISA (POSTN is the gene that encodes Periostin).

2. SPECIES – SPECIFICITY – CROSS REACTIVITY

Verify if the assay can be used in the respective model you will be measuring- e.g. human, or preclinical samples such as rat, mouse, monkey. Often ELISA kits can be used for various species, due to high homology between species. As an example the biomarker ELISA kit for NT-proANP was developed for measurements in human samples. Due to the high sequence homology between species, the kit is successfully used to measure NT-proANP as a cardiac safety biomarker in various animal models (rat, mouse, rabbit, monkey). 

3. SAMPLE TYPE

Which sample type (matrix) will you be using (e.g. EDTA-plasma, heparin-plasma, citrate-plasma, serum, cell culture supernatants, urine..) ?

Verify if the assay is compatible for your sample type and check the information in the protocol book. Also check if the assay validation was performed in the respective sample type you will be using. These data can often be found on the website of the assay manufacturer.

Important: the analysis of some biomarkers in the “wrong” sample matrix may lead to “false” results due to a matrix effect.

4. SAMPLE VOLUME

Verify the sample volume that will be required per well, consider duplicates when measuring your samples.

5. SENSITIVTY – BIOMARKER CONCENTRATIONS TO BE EXPECTED

The sensitivity of an ELISA assay refers to the lowest limit of detection (LOD) of the protein that can be detected with the antibody pair used in the ELISA kit. The sensitivity depends mainly on the affinity of the solid phase antibody (coating antibody). Therefore, using a high affinity antibody can increase sensitivity.

-Analytical sensitivity – limit of detection (LOD) is the lowest concentration that can be measured (detected) with statistical significance by means of a given analytical procedure. This concentration is calculated as the background +/- 2 standard deviations.

-Functional Sensitivity –  lower limit of detection (LLOQ) is the lowest concentration at which the analyte can be reliably detected.

How to select the right ELISA kit – before selecting an assay, study the validation data provided in the protocol booklet.

Some companies document the data on their respective website- product page. Documented reference values in an apparently healthy cohort and/or pathological values in serum and/or plasma of the analyte of interest may also be helpful to get an idea in which range sample values can be expected. It will be helpful to know which levels of the target protein can be expected in your respective sample. Sometimes samples require a pre-dilution step to assure that the signal falls within the dynamic range of the assay. Check the information in the protocol booklet if samples require a pre-dilution step and if the dilution buffer is included in the kit.

Of note: assays offering high sensitivity offer a different dynamic range than assays with a lower sensitivity.

    6. DYNAMIC RANGE

The dynamic range if an ELISA refers to the upper and lower range of concentrations of the target protein that the assay can accurately quantify.

Of note: the reported values given for the sensitivity and dynamic range of an assay can be misleading because they are often determined by using the standard protein (calibrators) in a assay buffer. However, this often does not represent the kinetic of detection of an endogenous protein /analyte in the biological sample.

7. ACCURACY / RECOVERY

The accuracy of an ELISA assay correctly identifies the presence or absence of the target protein/antigen (biomarker of interest) in a specific sample, which excludes matrix effects that may interfere with the measurement of the analyte of interest.

The accuracy (% recovery) is determined by spiking a biological sample (= sample matrix: serum, plasma-EDTA, heparin, citrate) with a known amount of the purified target protein. The spiked sample is then measured in the ELISA and the concentration is calculated from the standard curve. This calculated concentration is compared to the known concentration of the protein which is expressed as a percentage of recovery. As an example, a 90% recovery means that the measured concentration in the sample is 10% lower than the actual concentration of spiked protein in the sample. It suggests that the proteins and other molecules in the sample type did not interfere with the quantification of the protein.

8. ASSAY PERFORMANCE – ASSAY VALIDATION

Evaluation of the assay´s performance characteristics is important in choosing an ELISA kit.

Select an assay that has gone through a rigorous validation process. Data on the following performance characteristics should be available:

• Accuracy (% recovery) – detection of a protein biomarker in clinical samples (acceptance criteria: ≥ 80% recovery).
• Dilution linearity and parallelism  – recovery of the analyte of interest in diluted samples (acceptance criteria: ≤ 20% difference from undiluted samples)
• Specificity & cross-reactivity – making sure that you detect only the analyte of interest
• Precision – within-run (intra-assay) precision and in-between run (inter-assay) precision – ensuring precise and reproducible results within an across assay lots (acceptance criteria: ≤ 15%). The CV (%) or coefficient of variability shows how consistent the assay is.
• Calibration – ensures consistent performance over the range of the assay of the calibration curve
• Sample stability – ensures the stability of the analyte of interest (e.g. exposure of real samples to multiple freeze-thaw cycles, stability at room temperature..).
• Sensitivity – depends on the analyte of interest.
• Dynamic range– depends on the analyte of interest.
• Specificity – verify reactivity with highly homologous proteins
• Calibration – ensures consistent performance over the range of the assay of the calibration curve
• Sample stability – ensures the stability of the analyte of interest (e.g. exposure of real samples to multiple freeze-thaw cycles, stability at room temperature..).

 

9. COMPONENTS of the KIT

Verify if the content of the ELISA assay kit includes all the necessary components e.g. controls, assay dilution buffer. Consider storage requirements such as temperature sensitivity and expiration date.

10. REFERENCES &CITATIONS

Verify for available citations of the specific ELISA kit. These publications can usually be found on the manufacturer´s website.  

11. PRODUCT ORIGIN

Check the originator of the ELISA kit – who developed and manufactured the assay?  More and more kits are repacked and are sold under different brands, although it is always the same kit.

The originator of the ELISA kit will more likely give you qualified support as they “know” their product (e.g. availability of additional calibrators, controls, buffers.., technical know-how on the kit..).

12. CUSTOMER SUPPORT

Verify if the kit provider can provide timely and helpful customer service.

 

 

 

 

Literature

Characterization of a sandwich ELISA for the quantification of all human periostin isoforms.Gadermaier E, Tesarz M, Suciu AA, Wallwitz J, Berg G, Himmler G. J Clin Lab Anal. 2018 Feb;32(2):e22252. doi: 10.1002/jcla.22252. Epub 2017 May 11. PMID: 28493527; PMCID: PMC6816904.

 

Biomedica’s FGF23 ELISA kits now available for the US Biotech community at 25% trial discount.

FGF23 (fibroblast growth factor 23) is a 32 kDa protein with 251 amino acids that is proteolytically processed between arginine179 and serine180 to generate N-terminal and C-terminal fragments. FGF23 is mainly secreted by osteocytes and controls phosphate and 1,25(OH)2 vitamin D homeostasis. Epidemiological data suggest that higher FGF23 concentrations are associated with all-cause mortality, cardiovascular mortality, a higher risk of myocardial infarction, stroke and heart failure.
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FGF23 ELISA kits available for the US & CA

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Related kits: Sclerostin . OPG . Periostin . Vanin-1 . NT-proBNP . NT-proANP 

 

Literature

Non-Classical Effects of FGF23: Molecular and Clinical Features. Martínez-Heredia L, Canelo-Moreno JM, García-Fontana B, Muñoz-Torres M.Int J Mol Sci. 2024 Apr 30;25(9):4875. doi: 10.3390/ijms25094875. PMID: 38732094; PMCID: PMC11084844.

The role of fibroblast growth factor 23 in regulation of phosphate balance. Wilson R, Mukherjee-Roy N, Gattineni J. Pediatr Nephrol. 2024 Dec;39(12):3439-3451. doi: 10.1007/s00467-024-06395-5. Epub 2024 Jun 14. PMID: 38874635.

FGF23 signalling and physiology. Ho BB, Bergwitz C. J Mol Endocrinol. 2021 Feb;66(2):R23-R32. doi: 10.1530/JME-20-0178. PMID: 33338030; PMCID: PMC8782161.

World Cancer Day is a campaign to promote global awareness of cancer and to encourage its prevention, detection, and treatment. The day was initiated by the Union for International Cancer Control (UICC) in 2000 serving as a platform to promote research, improve education, and increase funding for cancer treatment and care.

World Cancer Day 

Key Statistics: The Global Impact of Cancer

Cancer is one of the foremost causes of mortality around the globe. In 2022, there were nearly 20 million new cases, and 9.7 million deaths attributed to cancer worldwide. Projections indicate that by 2040, the annual number of new cancer cases could reach 29.9 million, with cancer-related deaths increasing to 15.3 million.

In general, cancer rates tend to be highest in countries where populations enjoy greater life expectancy, educational attainment, and living standards. However, certain types of cancer, such as cervical cancer, show a contrasting trend, with the highest incidence found in countries where these measures are lower (1, 2).

Discover BIOMEDICA´s Biomarker ELISA kits for cancer research

Neuropilin-1, Periostin, Semaphorin 4D, Osteoprotegerin, RANKL, LRG1,  and others

 

Advantages of Biomedica ELISA assay kits

• RELIABLE – full validation package
  • CONVENIENT – assay range optimized for clinical samples
  • EASY – ready to use prediluted calibrators & controls
  • LOW sample volumes
  • TRUSTED – widely cited

 

Literature

1. https://www.cancer.gov/about-cancer/understanding/statistics
2. Cancer statistics for the year 2020: An overview. Int J Cancer. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray F. 2021 Apr 5. doi: 10.1002/ijc.33588. Epub ahead of print. PMID: 33818764.

 

Further reading

Influence of Diet and Nutrition on Prostate Cancer. Matsushita M, Fujita K, Nonomura N. Int J Mol Sci. 2020 Feb 20;21(4):1447. doi: 10.3390/ijms21041447. PMID: 32093338; PMCID: PMC7073095.

Abstract

The incidence of prostate cancer (PCa) displays widespread regional differences, probably owing to differences in dietary habits. Nutrients, including fat, protein, carbohydrates, vitamins (vitamin A, D, and E), and polyphenols, potentially affect PCa pathogenesis and progression, as previously reported using animal models; however, clinical studies have reported controversial results for almost all nutrients. The effects of these nutrients may be manifested through various mechanisms including inflammation, antioxidant effects, and the action of sex hormones. Dietary patterns including the Western and Prudent patterns also influence the risk of PCa. Recent studies reported that the gut microbiota contribute to tumorigenesis in some organs. Diet composition and lifestyle have a direct and profound effect on the gut bacteria. Human studies reported an increase in the abundance of specific gut bacteria in PCa patients. Although there are few studies concerning their relationship, diet and nutrition could influence PCa, and this could be mediated by gut microbiota. An intervention of dietary patterns could contribute to the prevention of PCa. An intervention targeting dietary patterns may thus help prevent PCa.

Breast cancer: A review of risk factors and diagnosis. Medicine (Baltimore). Obeagu EI, Obeagu GU 2024 Jan 19;103(3):e36905. doi: 10.1097/MD.0000000000036905. PMID: 38241592; PMCID: PMC10798762.

Abstract

Breast cancer remains a complex and prevalent health concern affecting millions of individuals worldwide. This review paper presents a comprehensive analysis of the multifaceted landscape of breast cancer, elucidating the diverse spectrum of risk factors contributing to its occurrence and exploring advancements in diagnostic methodologies. Through an extensive examination of current literature, various risk factors have been identified, encompassing genetic predispositions such as BRCA mutations, hormonal influences, lifestyle factors, and reproductive patterns. Age, family history, and environmental factors further contribute to the intricate tapestry of breast cancer etiology. Moreover, this review delineates the pivotal role of diagnostic tools in the early detection and management of breast cancer. Mammography, the cornerstone of breast cancer screening, is augmented by emerging technologies like magnetic resonance imaging and molecular testing, enabling improved sensitivity and specificity in diagnosing breast malignancies. Despite these advancements, challenges persist in ensuring widespread accessibility to screening programs, particularly in resource-limited settings. In conclusion, this review underscores the importance of understanding diverse risk factors in the development of breast cancer and emphasizes the critical role of evolving diagnostic modalities in enhancing early detection. The synthesis of current knowledge in this review aims to contribute to a deeper comprehension of breast cancer’s multifactorial nature and inform future directions in research, screening strategies, and preventive interventions.

Breast cancer is the most prevalent cancer among women globally. Enhancing our knowledge of how breast cancer develops, progresses, and metastasizes could aid in decreasing the risk and impact of the disease. Circulating proteins in serum or plasma can serve as biomarkers of cancer progression and prognosis while also serving as potential therapeutic targets. Enhancing our understanding on how cancers originate, grow and spread could aid in lowering the risk and impact of the disease. Recent research on cancer markers has highlighted novel protein biomarkers and promising therapeutic targets in breast cancer:

PERIOSTIN, NEUROPILIN-1, SEMAPHORIN 4D, and LEUCINE-RICH ALPHA-2-GLYCOPROTEIN. These proteins can be easily detected in human serum and plasma using ELISA assays.

Novel Biomarkers in Breast Cancer

PERIOSTIN (alternative names: POSTN, OSF-2, OSF2, PDLPN, PN)

Periostin is a matricellular protein that plays a significant role in various physiological and pathological processes, including tissue remodeling, inflammation, and wound healing. In the context of breast cancer, periostin has garnered attention due to its involvement in tumorigenesis, progression, and the tumor microenvironment.

Role of Periostin in Breast Cancer

Tumor Microenvironment: Periostin is often overexpressed in the extracellular matrix (ECM) of breast tumors (1). It interacts with various cells in the tumor microenvironment, including cancer-associated fibroblasts, immune cells, and endothelial cells, promoting tumor growth and metastasis. A recent study has demonstrated that Periostin drives extracellular matrix degradation, stemness, and chemoresistance in triple-negative breast cancer cells by activating specific signaling pathways (2).

Cell Signaling: Periostin can activate multiple signaling pathways that contribute to cancer progression. It is known to bind to integrins on the surface of cancer cells, which can lead to enhanced cell survival, proliferation, and migration. This signaling also supports processes such as epithelial-to-mesenchymal transition (EMT), a critical step in cancer metastasis.

Metastasis: Elevated levels of periostin have been associated with increased metastasis in breast cancer. Studies have indicated that higher periostin expression correlates with the aggressive behavior of breast cancer cells, particularly in triple-negative breast cancer (TNBC), which is known for its poor prognosis (3).

Periostin as a Potential Biomarker: Due to its association with poor outcomes and aggressive disease, periostin has been investigated as a potential biomarker for breast cancer. Its expression levels in tumor tissues or serum may provide insights into disease progression and treatment responses. Epithelial periostin expression is correlated with poor survival in patients with invasive breast carcinoma (3). High serum levels of Periostin have been demonstrated to be associated with poor survival in breast cancer (4).

Therapeutic Target: Given its role in promoting cancer progression, periostin presents a potential therapeutic target. Inhibition of periostin signaling may offer a novel strategy for treating aggressive breast cancer subtypes by disrupting the supportive tumor microenvironment (5).

Conclusion: Periostin plays a multifaceted role in breast cancer, affecting tumor growth, metastasis, and the tumor microenvironment. Its involvement in key molecular pathways and its potential utility as a biomarker make it a significant focus of ongoing research. Targeting periostin could open new avenues for therapy, particularly in aggressive forms of breast cancer, ultimately aiming to improve patient outcomes. Further studies are needed to fully elucidate its mechanisms and to evaluate its efficacy as a therapeutic target in clinical settings.

Periostin can reliably be measured in human blood samples with a conventional ELISA assay developed and manufactured by BIOMEDICA.

PERIOSTIN ELISA (cat. no. BI-20433)

• EASY – ready to use calibrators & controls included
• RELIABLE – validated according to international quality guidelines
• LOW sample volume- 10 µl / sample
• TRUSTED – widely cited

 

An in-depth characterization of the Biomedica Periostin ELISA has been published here: Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier E et al., J Clin Lab Anal. 2018; 32(2):e22252.

 

Novel Biomarkers in Breast Cancer

NEUROPILIN-1 (alternative names: NRP1, BDCA4, CD304, NP1, NRP, VEGF165R)

Neuropilin-1 (NRP1) is a transmembrane protein that has emerged as an important player in breast cancer biology. It is involved in various cellular processes, including cell signaling, survival, and migration, and has been implicated in cancer progression and metastasis (6).

Role of Neuropilin-1 in Breast Cancer

Tumor Growth and Survival: Neuropilin-1 (NRP1) is expressed in both cancer cells and the surrounding stromal cells within the tumor microenvironment. It has been linked to enhanced cell survival and proliferation, contributing to tumor growth. Elevated NRP1 expression has been associated with aggressive breast cancer subtypes, such as triple-negative breast cancer (TNBC) (6). A recent study has demonstrated that high NRP1 expression is associated with shorter relapse- and metastasis-free survival specifically in ER-negative BrCa cohorts (7).

Angiogenesis: NRP1 plays a critical role in angiogenesis, the formation of new blood vessels from existing ones, which is crucial for tumor growth and metastasis. By interacting with vascular endothelial growth factor (VEGF) and its receptors, NRP1 promotes endothelial cell proliferation and migration, facilitating the tumor’s ability to establish a blood supply (8).

Metastasis: Neuropilin-1 expression has been shown to be associated with lymph node metastasis in breast cancer tissues (9). Increased levels of NRP1 in breast cancer have been correlated with a higher propensity for metastasis. Studies have shown that NRP1 facilitates the migration of cancer cells to distant sites, contributing to the spread of the disease and poorer patient outcomes.

Potential Biomarker: In breast cancer patients, soluble Neuropilin-1 has shown to be an independent marker of poor prognosis in early breast cancer (10). In addition NRP-1 has also been shown to be a potential biomarker of prognosis and invasive-related parameters in other cancers such as liver and colorectal cancer (11).

Therapeutic Target: Given its involvement in tumor growth, angiogenesis, and metastasis, NRP1 is being explored as a therapeutic target. Strategies to inhibit NRP1 function or block its signaling pathways could offer new avenues for breast cancer treatment, particularly for patients with aggressive or metastatic disease (12).

Conclusion: Neuropilin-1 is a significant factor in the biology of breast cancer, influencing tumor growth, metastasis, and interactions within the tumor microenvironment. Its role in promoting angiogenesis and facilitating aggressive cellular behaviors makes it an important target for ongoing research. Targeting NRP1 could provide new therapeutic approaches for breast cancer, potentially improving outcomes for patients, especially those with more aggressive forms of the disease. Further studies are needed to clarify its mechanisms and evaluate targeted therapies in clinical settings.

Neuropilin-1 (NRP1) can reliably be measured in human blood samples with a conventional ELISA assay developed and manufactured by BIOMEDICA.

Total soluble NEUROPILIN-1 ELISA (cat. no. BI-20409)

• EASY – ready to use calibrators & controls included
• RELIABLE – validated according to international quality guidelines
• LOW sample volume- 10 µl / sample
• TRUSTED – for citations click here

 

The Biomedica human NRP-1 ELISA is described in this following publication: Characterization of a sandwich ELISA for quantification of total human soluble neuropilin-1. Gadermaier E, Tesarz M, Wallwitz J, Berg G, Himmler G. J Clin Lab Anal. 2019; 33(7):e22944. doi: 10.1002/jcla.22944. PMID: 31219204.

 

Novel Biomarkers in Breast Cancer

SEMAPHORIN 4D (alternative names: Sema4D, C9orf164, SEMAJ, CD100, BB18, GR3, CD100, COLL4)

Semaphorin 4D (Sema4D) is a member of the semaphorin family of proteins, which are known for their roles in cell signaling, axon guidance, and immune regulation (13). In the context of breast cancer, Sema4D has garnered attention for its involvement in tumor growth, metastasis, and the tumor microenvironment.

About Semaphorin 4D in Breast Cancer

Tumor Growth and Progression: Sema4D can influence the behavior of cancer cells, promoting survival and proliferation. It may also aid in the establishment of a supportive tumor microenvironment. In a study researchers have shown that Sema4D was expressed at higher levels in breast cancer cell lines compared with the normal human breast epithelial cell lines (14).

Angiogenesis: Sema4D is involved in the formation of new blood vessels (angiogenesis), which is vital for tumor growth. It can modulate the activity of endothelial cells, thereby supporting the vascularization of tumors (14).

Immune Evasion: Sema4D can affect the immune response to tumors. It may contribute to the suppression of T-cell responses, allowing cancer cells to evade immune detection and destruction.

Metastasis: The expression of Sema4D has been linked to increased metastatic potential in breast cancer. It may facilitate the migration and invasion of cancer cells to distant sites in the body. In a recent study researchers have found that Semaphorin 4D promotes skeletal metastasis in breast cancer (15).

A decreased expression of semaphorin 4D and plexin-B in breast cancer has been shown to be associated with recurrence and poor prognosis in a breast cancer cohort (16).

Biomarker Potential: Research suggests that Sema4D levels could serve as a potential biomarker for breast cancer progression and prognosis, although further studies would be needed to establish its clinical utility.

The potential link between Sema4D and estrogen receptor signaling was proposed in a study measuring circulating Sema4D plasma levels at primary diagnosis and in a follow-up sample 12 months after surgery in a cohort of 46 pre- and postmenopausal women with primary estrogen receptor positive breast cancer receiving adjuvant tamoxifen. The finding potentially represents an additional mechanism of the bone-protective properties of tamoxifen (17).

Therapeutic Targeting:  Due to its involvement in various aspects of cancer biology, Sema4D is being explored as a potential therapeutic target. Inhibiting its function might help in reducing tumor growth and improving the effectiveness of existing treatments. A study demonstrated that a Sema4D antibody in combination with either CTLA-4 or PD-1 blockade enhanced rejection of tumors or tumor growth delay, resulting in prolonged survival with either treatment (18).

Conclusion: Sema4D plays a multifaceted role in breast cancer pathology, influencing tumor growth, metastasis, and immune interactions. Ongoing research is essential to fully understand its mechanisms and to explore its potential as a target for therapeutic intervention.

Soluble SEMAPHORIN 4D ELISA (cat. no. BI-20405)

• EASY – ready to use calibrators & controls included
• RELIABLE – first validated according to international quality guidelines
• LOW sample volume- 10 µl / sample – no predilution!
• Reference values for healthy individuals provided

 

An in-depth characterization of the Biomedica Semaphorin 4D ELISA has been published here: A high-sensitivity enzyme immunoassay for the quantification of soluble human semaphorin 4D in plasma. Laber, A., Gadermaier, E., Wallwitz, J., Berg, G., Himmler, G., 2019. Anal. Biochem. 574, 15–22.  PMID: 30879960

 

Novel Biomarkers in Breast Cancer

LEUCINE-RICH ALPHA-2-GLYCOPROTEIN (alternative names: LRG, LRG1, HMFT1766) 

Leucine-rich alpha-2-glycoprotein (LRG) is a protein that has been studied in various diseases, including cancer. It is known for its involvement in inflammation and immune responses. In the context of breast cancer, LRG has attracted interest for its potential role as a biomarker and its involvement in the tumor microenvironment. For more information on LRG-1 as a prognostic marker for breast cancer survival please click here

LRG ELISA Assay Highlights (cat. no. BI-LRG)

• CONVENIENT – ready to use reagents and controls included
• RELIABLE – rigorously validated following international quality guidelines
• EASY – results available in 3 hours

 

Related products

DKK-1 (Dickkopf-1) ELISA kit (cat. no. BI-20413) 

• Direct measurement – no sample pre-dilution
• Day test – all reagents included
• Widely cited +180 references!

 

Literature 

1.  Expression of periostin in breast cancer cells. Ratajczak-Wielgomas K, Grzegrzolka J, Piotrowska A, Matkowski R, Wojnar A, Rys J, Ugorski M, Dziegiel P. Int J Oncol. 2017; 51(4):1300-1310. doi: 10.3892/ijo.2017.4109.
2. Periostin drives extracellular matrix degradation, stemness, and chemoresistance by activating the MAPK/ERK signaling pathway in triple-negative breast cancer cells. Wu J, Li J, Xu H, Qiu N, Huang X, Li H. Lipids Health Dis. 2023; 16;22(1):153. doi: 10.1186/s12944-023-01912-1.
3. Epithelial periostin expression is correlated with poor survival in patients with invasive breast carcinoma. Kim GE, Lee JS, Park MH, Yoon JH. PLoS One. 2017; 21;12(11):e0187635. doi: 10.1371/journal.pone.0187635. PMID: 29161296..
4. High serum levels of periostin are associated with a poor survival in breast cancer. Rachner TD et al., Breast Cancer Res Treat. 2020; 180(2):515-524.
5. Development of an engineered peptide antagonist against periostin to overcome doxorubicin resistance in breast cancer. Oo KK, Kamolhan T, Soni A, Thongchot S, Mitrpant C, O-Charoenrat P, Thuwajit C, Thuwajit P. BMC Cancer. 2021; 14;21(1):65. doi: 10.1186/s12885-020-07761-w.
6. Neuropilin1, a novel independent prognostic factor and therapeutic target in triple-negative breast cancer. Wang H, Zhang YN, Xu DQ, Huang JG, Lv D, Shi XY, Liu JY, Ren HW, Han ZX. Neoplasma. 2020; 67(6):1335-1342. doi: 10.4149/neo_2020_191127N1223. PMID: 32657612.
7. Neuropilin-1 is over-expressed in claudin-low breast cancer and promotes tumor progression through acquisition of stem cell characteristics and RAS/MAPK pathway activation. Tang YH, Rockstroh A, Sokolowski KA, Lynam LR, Lehman M, Thompson EW, Gregory PA, Nelson CC, Volpert M, Hollier BG. Breast Cancer Res. 2022; 25;24(1):8. doi: 10.1186/s13058-022-01501-7. PMID: 35078508.
8. Endothelial VEGFR Coreceptors Neuropilin-1 and Neuropilin-2 Are Essential for Tumor Angiogenesis. Benwell CJ, Johnson RT, Taylor JAGE, Price CA, Robinson SD. Cancer Res Commun. 2022 Dec 14;2(12):1626-1640. doi: 10.1158/2767-9764.CRC-22-0250. PMID: 36970722; PMCID: PMC10036134.
9. Neuropilin-1 expression is associated with lymph node metastasis in breast cancer tissues. Seifi-Alan M, Shams R, Bandehpour M, Mirfakhraie R, Ghafouri-Fard S. Cancer Manag Res. 2018 Jul 11;10:1969-1974. doi: 10.2147/CMAR.S169533. PMID: 30022855; PMCID: PMC6045910.
10. Soluble Neuropilin-1 is an independent marker of poor prognosis in early breast cancer. Rachner TD, Kasimir-Bauer S, Goebel A, Erdmann K, Hoffmann O, Rauner M, Hofbauer LC, Kimmig R, Bittner AK. J Cancer Res Clin Oncol. 2021; 147(8):2233-2238. doi: 10.1007/s00432-021-03635-1. PMID: 33884469.
11. Neuropilin-1 as a Potential Biomarker of Prognosis and Invasive-Related Parameters in Liver and Colorectal Cancer: A Systematic Review and Meta-Analysis of Human Studies. Fernández-Palanca P, Payo-Serafín T, Fondevila F, Méndez-Blanco C, San-Miguel B, Romero MR, Tuñón MJ, Marin JJG, González-Gallego J, Mauriz JL. Cancers (Basel). 2022 Jul 15;14(14):3455. doi: 10.3390/cancers14143455. PMID: 35884516.
12. SPECT and near-infrared fluorescence imaging of breast cancer with a neuropilin-1-targeting peptide. Feng GK, Liu RB, Zhang MQ, Ye XX, Zhong Q, Xia YF, Li MZ, Wang J, Song EW, Zhang X, Wu ZZ, Zeng MS.J Control Release. 2014; 28;192:236-42. doi: 10.1016/j.jconrel.2014.07.039. PMID: 25058570.
13. Semaphorin 4D as a guidance molecule in the immune system. Kuklina E. Int Rev Immunol. 2021;40(4):268-273. doi: 10.1080/08830185.2021.1905807. PMID: 33787446.
14. The role of semaphorin 4D in tumor development and angiogenesis in human breast cancer. Jiang H, Chen C, Sun Q, Wu J, Qiu L, Gao C, Liu W, Yang J, Jun N, Dong J. Onco Targets Ther. 2016 Sep 26;9:5737-5750. doi: 10.2147/OTT.S114708. PMID: 27729799; PMCID: PMC5045906.
15. Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer. Yang YH, Buhamrah A, Schneider A, Lin YL, Zhou H, Bugshan A, Basile JR.PLoS One. 2016; 11(2):e0150151. doi: 10.1371/journal.pone.0150151. PMID: 26910109.
16. Reduced expression of semaphorin 4D and plexin-B in breast cancer is associated with poorer prognosis and the potential linkage with oestrogen receptor. Malik MF, Ye L, Jiang WG. Oncol Rep. 2015 Aug;34(2):1049-57. doi: 10.3892/or.2015.4015. Epub 2015 May 28. PMID: 26035216.
17. Plasma levels of Semaphorin 4D are decreased by adjuvant tamoxifen but not aromatase inhibitor therapy in breast cancer patients. Göbel, A., Kuhlmann, J.D., Link, T., Wimberger, P., Link-Rachner, C., Thiele, S., Dell’Endice, S., Furesi, G., Breining, D., Rauner, M., Hofbauer, L.C., Rachner, T.D., 2019. Journal of Bone Oncology, 16: 100237. PMID: 31011525
18. Semaphorin4D Inhibition Improves Response to Immune-Checkpoint Blockade via Attenuation of MDSC Recruitment and Function. Clavijo PE, Friedman J, Robbins Y, Moore EC, Smith E, Zauderer M, Evans EE, Allen CT. Cancer Immunol Res. 2019; 7(2):282-291. doi: 10.1158/2326-6066.CIR-18-0156. PMID: 30514791.

Join us at the ASBMR (American Society of Bone and Mineral Research) Conference at booth number 145. The annual meeting is taking place in Toronto, ON, Canada from September 27-30, 2024.

The American Society of Bone and Mineral Research (ASBMR) meeting is considered to be the largest event worldwide covering fields in bone, mineral and musculoskeletal research. The meeting attracts over 2,500 participants across the globe, including both clinicians and researchers working in different disciplines and at all career levels. The meeting provides attendees with exciting opportunities to exchange knowledge and to learn about the latest scientific and medical advances in the field.

Discover some of our biomarker assays for clinical research in bone and mineral disorders

–FGF23 intact and c-terminal

–Sclerostin and bioactive Sclerostin

–Osteoprotegerin(OPG)  and soluble RANKL

–Dickkopf-1 and Periostin

 

 

Exploring Biomarkers in Bone Biology

During the process of bone remodeling, bone cells release biomarkers that can aid in the evaluation of bone diseases and serve as valuable therapeutic targets. These bone biomarkers can be readily detected in serum and plasma samples using immunoassays.

A recent review by Nicolas H Hart et al., provides researchers and clinicians involved in bone and mineral metabolism with a comprehensive contemporary update on the Biological basis of bone strength: anatomy, physiology and measurement. J Musculoskelet Neuronal Interact. 2020; ;20(3):347-371.

Abstract

Understanding how bones are innately designed, robustly developed and delicately maintained through intricate anatomical features and physiological processes across the lifespan is vital to inform our assessment of normal bone health, and essential to aid our interpretation of adverse clinical outcomes affecting bone through primary or secondary causes. Accordingly this review serves to introduce new researchers and clinicians engaging with bone and mineral metabolism, and provide a contemporary update for established researchers or clinicians. Specifically, we describe the mechanical and non-mechanical functions of the skeleton; its multidimensional and hierarchical anatomy (macroscopic, microscopic, organic, inorganic, woven and lamellar features); its cellular and hormonal physiology (deterministic and homeostatic processes that govern and regulate bone); and processes of mechanotransduction, modelling, remodelling and degradation that underpin bone adaptation or maladaptation. In addition, we also explore commonly used methods for measuring bone metabolic activity or material features (imaging or biochemical markers) together with their limitations.

 

 

 

We are excited to be soon exhibiting at the International Conference on Children’s Bone Health (ICCBH) in Salzburg, Austria from June 22-25, 2024.

Join us at booth number 4 and explore our widely trusted Biomarker ELISA Assay Kits including Fibroblast Growth Factor (FGF23), Sclerostin, Periostin, NT-proCNP, and many others.

We look forward to connecting with you!

Join us at the International Conference on Children’s Bone Health

Click here for more information about the conference for anyone who is interested in 

bone metabolism and bone mass in children, adolescents and young adults.

The ICCBH conference aims to unite researchers, clinicians, health professionals, and others from different fields to gain an understanding of the developing skeleton with regards to childhood health and disease. Latest advancements, innovative therapies, and genetic discoveries will be discussed.

More about Biomarkers in Bone Biology  

Bone cells release biomarkers during bone remodeling. They can be used in assessing bone diseases and represent useful therapeutic targets. Bone biomarkers can easily be detected in serum and plasma samples by immunoassay.  

A recent review by Ponds-Belda OD et al., Mineral Metabolism in Children: Interrelation between Vitamin D and FGF23 focuses on various aspects of FGF23 metabolism in children, reference values,  and other key variables involved in mineral homeostasis. 

BIOMEDICA offers quality kits to measure various bone biomarkers 

Sclerostin ELISA (SOST; cat.no. BI-20492)  

OPG ELISA (Osteoprotegerin; cat.no. BI-20403)  

RANKL ELISA (soluble RANKL; cat.no. BI-20462)  

DKK-1 ELISA (Dickkopf-1; cat.no. BI-20413)  

FGF23 intact ELISA (Fibroblast growth factor-23 intact; cat.no. BI-20700) 

FGF23 C-terminal ELISA (Fibroblast growth factor-23 C-terminal; cat.no. cat.no. BI-20702) 

PERIOSTIN ELISA (POSTN, BI-20433) 

NT-proCNP ELISA (NT-C-type natriuretic peptide, BI-20812)

 TRUSTED – cited in over 1300 publications

• Kit validations follows international quality guidelines
• Developed & manufactured by Biomedica in Austria

Chronic kidney disease is a progressive condition that affects >10% of the general population worldwide (1). Current clinical biomarkers prove effective at advanced stages of renal impairment, limiting the timely initiation of potentially successful therapeutic interventions. There is an unmet need for more refined biomarkers capable of detecting CKD at earlier stages, thereby enhancing the prospects for patients’ outcomes.

In the last decade, the advancement in the fields of genomics, proteomics, and metabolomics have led to the identification of potential biomarker candidates that may offer important diagnostic and prognostic information in patients suffering from kidney diseases (2).

Among the current established biomarkers such as serum creatinine, albuminuria, and proteinuria, novel biomarkers for kidney diseases could potentially provide additional prognostic information. They could help to predict treatment response in various clinical settings such as acute kidney injury, transplant rejection or glomerulopathies (2).

Emerging Biomarkers in Kidney Disease

Biomedica offers a range of ELISA assay kits to reliably detect biomarkers in blood samples of patients with kidney diseases.

Endostatin, Vanin-1, Periostin, FGF23, IL-6 and more…

 

 

ENDOSTATIN – a potential biomarker of renal fibrosis, chronic kidney disease (CKD), prognostic marker in acute kidney injury (AKI)

Endostatin is an extracellular matrix protein which is expressed in patients during the progression of renal fibrosis. The significant increase of serum Endostatin levels may be due to the enhanced degradation of the extracellular matrix in patients with chronic kidney disease (3, 4). Endostatin has also been studied as a prognostic marker in patients with acute kidney injury (AKI) (5) and is independently associated with incident cardiovascular events in CKD patients (6).

Endostatin can reliably be quantified in serum, plasma and urine samples:

• Endostatin ELISA | BI-20742
• Endostatin ELISA (Mouse/Rat) | BI-20742MR  (7)

 

VANIN-1 – a potential biomarker of acute kidney injury and drug induced renal injury

Vascular non-inflammatory molecule-1 (Vanin-1) is highly expressed in the kidney (8) and has been proposed as a marker in acute kidney injury and drug induced renal injury (9).  Vanin-1 has been identified as a marker of kidney damage as shown n a rat model of type 1 diabetic nephropathy (10).

Urinary Vanin-1  has been investigated in children with renal fibrosis (11) and as a predictor of acute pyelonephritis in young children with urinary tract infection (12). A recent study investigated the role of urinary Vanin-1 in kidney transplant recipients (13).

Vanin-1 can easily be measured with a conventional ELISA assay:

• Vanin-1 (urine) ELISA | BI-VAN1U
• Vanin-1 ELISA (Mouse/Rat) ELISA | BI-VAN1MR        

 

PERIOSTIN – a potential early biomarker of renal tubular injury

Periostin is a matricellular protein that is involved in tissue remodeling and wound healing. Studies have demonstrated that the expression of Periostin in the kidney correlates with the degree of interstitial fibrosis and a decline in kidney function (15). Elevated urine Periostin levels were found in patients with type 2 diabetes which were present before the onset of microaluminuria. The authors proposed that urinary Periostin could be an early biomarker of renal tubular injury (16).

Periostin can reliably be measured in serum, plasma, and urine samples with a fully validated ELISA assay (17).

• Periostin ELISA | BI-20422
• Periostin ELISA (Mouse/Rat) | BI-20433MR

 

FGF23 – a potential early biomarker cardiovascular events in patients with renal-cardiovascular disease

Fibroblast growth factor 23 (FGF23) is an endocrine hormone that regulates phosphate homeostasis by modulating renal phosphate reabsorption in the kidney. Circulating FGF23 increases with declining kidney function and high FGF23 and phosphate levels are related to cardiovascular disease and mortality (18, 19). 

• FGF23  (C-terminal) multimatrix ELISA | BI-20702
• FGF23 Intact ELISA | BI-20700

 

IL-6 – a biomarker of inflammation

 Interleukin-6 (IL-6) is a cytokine that plays a crucial role in inflammation and in the regulation of immune response. It is a signaling molecule that is involved in various physiological processes, including the activation of immune cells and the coordination of responses to infections or injury. IL-6 is implicated in diseases where inflammation is a prominent feature (20).

•  IL-6 ELISA | BI-IL6
• HIGHLY SENSITIVE – measurable values in serum and plasma samples
• EASY – ready to use calibrators and controls

 

 

Literature

1.  Epidemiology of chronic kidney disease: an update 2022. Kovesdy CP. Kidney Int Suppl (2011). 2022. 12(1):7-11. doi: 10.1016/j.kisu.2021.11.003. PMID: 35529086; PMCID: PMC9073222.
2. Emerging Biomarkers for Early Detection of Chronic Kidney Disease. Mizdrak M, Kumrić M, Kurir TT, Božić J. J Pers Med. 2022. 12(4):548. doi: 10.3390/jpm12040548. PMID: 35455664.
3. A defective angiogenesis in chronic kidney disease. Futrakul N, Butthep P, Laohareungpanya N, Chaisuriya P, Ratanabanangkoon K. Ren Fail. 2008. 30(2):215-7. doi: 0.1080/08860220701813335. PMID: 18300124.
4. Endostatin in Renal and Cardiovascular Diseases. Li M, Popovic Z, Chu C, Krämer BK, Hocher B., Kidney Dis (Basel). 2021.9;7(6):468-481. doi: 10.1159/000518221. PMID: 34901193.
5. Prognostic value of dynamic plasma endostatin for the prediction of mortality in acute kidney injury: A prospective cohort study. Jia HM, Zheng Y, Han Y, Ma WL, Jiang YJ, Zheng X, Guo SY, Zhang TE, Li WX., J Int Med Res. 2020.  48(7):300060520940856. PMID: 32691651.
6. Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival. Kanbay M, Afsar B, Siriopol D, Unal HU, Karaman M, Saglam M, Gezer M, Taş A, Eyileten T, Guler AK, Aydin İ, Oguz Y, Tarim K, Covic A, Yilmaz MI. Eur J Intern Med. 2016. 33:81-7. doi: 10.1016/j.ejim.2016.06.033. PMID: 27394925.
7. Validation of an enzyme-linked immunosorbent assay (ELISA) for quantification of endostatin levels in mice as a biomarker of developing glomerulonephritis. Wallwitz J, Aigner P, Gadermaier E, Bauer E, Casanova E, Bauer A, Stoiber D. PLoS One. 2019. 14(8):e0220935. doi: 10.1371/journal.pone.0220935. PMID: 31404120.
8. Chemical biology tools to study pantetheinases of the vanin family. Schalkwijk, J, Jansen, P. Biochem Soc Trans. 2014. 42, 1052–1055.
9. Urinary Vanin-1 As a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury. Hosohata K et al.J  Pharm  Exp Ther. 2012. 341, 656–662.
10. Proteomic identification of vanin-1 as a marker of kidney damage in a rat model of type 1 diabetic nephropathy. Fugmann T et al., Kidney Int. 2011. 80, 272–281.
11. The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis-A Pilot Study. Mizerska-Wasiak M, Płatos E, Cichoń-Kawa K, Demkow U, Pańczyk-Tomaszewska M. J Clin Med. 2022. 11(5):1265. doi: 10.3390/jcm11051265. PMID: 35268356. 
12. Urinary vanin-1 for predicting acute pyelonephritis in young children with urinary tract infection: a pilot study. Krzemień G, Pańczyk-Tomaszewska M, Górska E, Szmigielska A. Biomarkers. 2021. 26(4):318-324.
13. Urinary vanin-1, tubular injury, and graft failure in kidney transplant recipients. Alkaff FF, Kremer D, Niekolaas TM, van den Born J, Rimbach G, Tseng TL, Berger SP, Bakker SJL, de Borst MH. Sci Rep. 2024. 4(1):2283. doi: 10.1038/s41598-024-52635-x. PMID: 38280883.
14. Development of an immunoassay that reveals altered uninary Vanin-1 in human with kidney disease. Wallwitz, J., Eichinger, B., Berg, G., Gadermaier, E., Himmler, G. 2018. Nephrology Dialysis Transplantation, Volume 33, Issue suppl_1, Page i126. 
15. Periostin in the Kidney. Wallace DP et al., Adv Exp Med Biol. 2019, 1132:99-112.
16. Periostin as a tissue and urinary biomarker of renal injury in type 2 diabetes mellitus. Satirapoj B et al., PLoS One. 2015, 17;10(4):e0124055.
17. Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier E et al., J Clin Lab Anal. 2018, 32(2):e22252.
18. Higher fibroblast growth factor-23 increases the risk of all-cause and cardiovascular mortality in the community. Ärnlöv J, Carlsson AC, Sundström J, Ingelsson E, Larsson A, Lind L, Larsson TE.  Kidney Int. 2013. 83(1):160-6. doi: 10.1038/ki.2012.327. PMID: 22951890. 
19. Fibroblast growth factor-23, cardiovascular prognosis, and benefit of angiotensin-converting enzyme inhibition in stable ischemic heart disease. Udell JA, Morrow DA, Jarolim P, Sloan S, Hoffman EB, O’Donnell TF, Vora AN, Omland T, Solomon SD, Pfeffer MA, Braunwald E, Sabatine MS. J Am Coll Cardiol. 2014. 10;63(22):2421-8, doi: 10.1016/j.jacc.2014.03.026. PMID: 24727254; PMCID: PMC4213068.
20. Interleukin 6 and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Chronic Coronary Syndrome. Batra G, Ghukasyan Lakic T, Lindbäck J, Held C, White HD, Stewart RAH, Koenig W, Cannon CP, Budaj A, Hagström E, Siegbahn A, Wallentin L; STABILITY Investigators. JAMA Cardiol. 2021. 6(12):1440-1445. doi: 10.1001/jamacardio.2021.3079. PMID: 34431970; PMCID: PMC8387946.
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Breast cancer is the most common detected cancer worldwide with 2.3 million new cases and 685, 000 deaths in 2020 (1).

1 in 8 women are predicted to be diagnosed with breast cancer in their lifetime. 

Early detection of breast cancer is the key to successful outcomes.

Breast Cancer Awareness Month – October 2023

Find out more about some of the different breast cancer associations worldwide and learn about what you should be aware of:

• National Breast Cancer Foundation Inc
• WHO Europe
• Breast Cancer UK
• Breast Cancer Foundation New Zealand
• Canadian Cancer Society
• Africa Health Organisation
• American Association for Cancer Research
• Japanese Breast Cancer Society

 

BIOMEDICA – Biomarker ELISA Kits for Breast Cancer Research

PERIOSTIN ▪ NEUROPILIN-1 ▪ OSTEPROTEGERIN ▪ soluble RANKL ▪ SEMAPHORIN 4D

check out our Brochure Biomarker ELISAs in Oncology

Assay Kit Highlights

√  EASY –ready to use calibrators & controls included (color-coded reagents)
√  FULL VALIDATION PACKAGE – assays are optimized for clinical samples
√   HIGH QUALITY GUARANTEED – results you can rely on
√  WIDELY CITED in 1500 + publications
√  COMPETENT CUSTOMER SERVICE

 

BIOMEDICA – Complete ready-to-use ELISA kits for superior performance and reproducibility

Literature

1. Current and future burden of breast cancer: Global statistics for 2020 and 2040. Arnold M, Morgan E, Rumgay H, Mafra A, Singh D, Laversanne M, Vignat J, Gralow JR, Cardoso F, Siesling S, Soerjomataram I Breast. 2022 Dec;66:15-23. doi: 10.1016/j.breast.2022.08.010. Epub 2022 Sep 2. PMID: 36084384; PMCID: PMC9465273.
2. The prevention and treatment of breast cancer- related lymphedema: A review. McEvoy MP, Gomberawalla A, Smith M, Boccardo FM, Holmes D, Djohan R, Thiruchelvam P, Klimberg S, Dietz J, Feldman S. Front Oncol. 2022 Dec 6;12:1062472. doi: 10.3389/fonc.2022.1062472. PMID: 36561522; PMCID: PMC9763870.
3. Breast Cancer in India: Screening, Detection, and Management. Bhardwaj PV, Dulala R, Rajappa S, Loke C. Hematol Oncol Clin North Am. 2023 Jun 15:S0889-8588(23)00069-2. doi: 10.1016/j.hoc.2023.05.014. Epub ahead of print. PMID: 37330342.
4. Outcomes in breast cancer-does ethnicity matter? Yap YS ESMO Open. 2023 Jun;8(3):101564. doi: 10.1016/j.esmoop.2023.101564. Epub 2023 Jun 7. PMID: 37290358; PMCID: PMC10265619.

 

 

We are scientists, developers and manufacturers and understand the importance of offering assays that generate specific, reliable and reproducible results.

Early on, starting from product development to final assay validation and product release until final ELISA kit manufacturing, every assay goes through a stringent quality control process.

Why choose ELISA assays from Biomedica?

Because we care!

Get the most accurate results from your precious samples with Biomedica ELISA kits.

   

 

SPECIFICIC – RELIABLE – REPRODUCIBLE ELISA Assays

 1. SPECIFICITY – epitope-mapped and characterized antibodies for accurate biomarker detection.

The performance of an ELISA is linked to the quality of the antibody pairs used for biomarker detection.

We therefore:

• select antibody pairs with high affinity and specificity with mapped binding sites
• optimize our assays to quantify biomarkers in both healthy and pathological samples

 

Example: FGF23 sample values of normal and pathological samples

2. RELIABILITY – extensive validation using clinical samples (parallelism, S/R, precision, analyte stability..) in various sample matrices

We validate our ELISA assays according to international quality guidelines (FDA, EMEA) .

Our Biomedica Immunassays go through an extensive validation process 

2.1. Accuracy – accurate detection of biomarkers in clinical samples and exclusion of matrix effects that may interfere with the measurement of the analyte of interest.

• Accuracy is determined in all validated sample types that are spiked with known amounts of the recombinant analyte. Samples are  analysed against the standard/calibration curve of the assay and then compared with the nominal value.

 

2.2. Parallelism / Dilution Linearity – lot to lot consistency ensured by our stringent quality management guidelines

• During assay validation we analyze the recovery of the analyte in diluted samples that contains the endogenous / recombinant analyte of interest.

 

Example: dilution linearity (parallelism) of samples containing endogenous and recombinant Neuropilin-1 (NRP1).

2.3. Specificity and Cross-Reactivity – only detects the analyte of interest

• We carefully select antibodies that exclusively detect the specific analyte. Our specificity experiments are designed to characterize the antibody-antigen interactions and to determine possible isoforms that could be bound by the antibody.

 

Example: antibody recognizing all three isoforms of the target analyte on a Western blot.

 

2.4. Sensitivity

• Our ELISA assays are optimized to minimize the background signal while maximizing the signals from the measurements of the analyte ensuring maximal sensitivity.

The data for the Lower Limit of Quantification (LLOQ) and the Limit of Detection (LOD) are indicted in the instructions for use and on our website for all our ELISA kits.

2.5. Precision – precise and reproducible results within and across lots

• Within-run and in-between run precision is tested several times within one ELISA assay lot to guarantee that results are accurate when using kits that derive from different lots.

2.6. Calibration

• The accurate quantification of a biomarker depends on the linearity and the reproducibility of the standard curve. During the assays optimization process we ensure low variability between the results of the calibrators. Where available, we employ WHO reference reagents to ensure a harmonized standardization.

 

Example: standard curve for the FGF23 ELISA after 4PL transformation. The error bars reflect the variability of the measurement.

2.7. Stability

• During development we test the stability of all assay components as well as the stability of the analyte of interest in the respective sample matrices (serum, plasma). For instance we expose real clinical samples with elevated levels of the analyte to multiple freeze-thaw cyles and also determine stability at room temperature.

 

Example: stability of the analyte Periostin in clinical samples after multiple freeze-thaw (F/T) cycles in different sample matrices.

 

Freeze-thaw stability of Periostin

 

Validation reports

The validation reports of the respective ELISA assays can be  downloaded on the individual Biomedica ELISA product pages.

 

3. REPRODUCIBILITY

 ELISA ASSAY QUALITY MANAGEMENT

 Our Quality Control Process

All our kits undergo a stringent quality control process, including testing of lot-to-lot consistency as well as the kit stability during shelf-life.

Our manufacturing process follows the ISO 9001: 2015 management system and conforms to GMP /GLP guidelines.

Ensuring lot-to-lot consistency with a panel of quality control samples

Our internal quality control panel is one integral part of our manufacturing protocols. It contains samples from different matrices (serum, EDTA-plasma, citrate-plasma..) containing the endogenous/natural analyte as well as samples spiked with the recombinant protein. Every new lot as well as all retains, that are assayed every three months, are tested with the specific QC sample panel.

Example:  IC trending showing the quotient of the proANP concentration measured in Internal Controls (IC) in 3 different proANP ELISA lots compared with previously established median concentrations.

 

 

 

Qualified CUSTOMER SERVICE – we accompany you in every step.

Our qualified customer service representatives have hands-on research experience to assist you along the way, from decision making to technical questions.

WE VALUE YOUR OPINION

Our ELISA assays are developed to serve your needs. We therefore select our biomarker targets based on your input. 

Pre-testing: before a new ELISA assay is launched,  selected customers test the product to ensure that the assay is reliable and reproducible outside of our lab-facilities. 

Biomedica – ELISA development scheme  

 

Learn more about how we guarantee the performance of our products – click here .

 

Further reading

ICH Q2(R2) Validation of analytical procedures – Scientific guideline

 

Biomedica features FGF23 ELISA – intact and C-terminal – assays

Meet us at the OSTEOLOGIE Conference taking place from 22-24 June 2023 in Salzburg, Austria! We will exhibit at booth # 36 introducing our novel biomarker ELISA assays to investigate bone and cancer induced bone diseases (e.g. Periostin, Semaphorin 4D, LRG, and others).

Our focus will also be on FGF23, an important regulator of renal phosphate handling, with our FGF23 intact and FGF23 C-terminal ELISA assays.

Drop by – we’d love to see you there!

Related products:

DKK-1 ELISA
OPG ELISA
free sRANKL ELISA
osteomiR – miRNA bone biomarker
FluoBolt Klotho FIA
Testing Services (ELISA, Luminex, miRNA)

 

Biomarkers & Bone Health – ELISA Kits for Clinical Research

Bone remodeling is a continuous process that removes bone and replaces it with newly synthesized bone. This bone turnover process preserves the mechanical function of the human skeleton.

Bone turnover biomarkers, e.g. markers of bone formation and bone resorption, have been used during the last decade to monitor bone diseases and to monitor their treatment.

Many of these markers are secreted by osteoblasts and osteoclasts and include regulators of bone turnover e.g. receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG).  

Though RANKL and OPG  play an integral role in bone turnover, they do not reflect the activity of osteocytes, the most abundant cell type in the bone.

Osteocytes are cells that regulate bone remodeling. They secrete proteins – bone regulation markers – that include Sclerostin (SOST), Dickkopf-1 (DKK-1), and Fibroblast growth factor  (FGF23). These markers reflect the osteocyte activity.

The above listed biomarkers circulate and can be measured in serum and plasma allowing the investigation of complex interactions between the bone and their relationship with other organs.

BIOMEDICA ELISA KITS – Biomarkers & Bone Health

check out our Bone Biomarker Brochure

ELISA Assay Kit Highlights

+ EASY – ready to use calibrators & controls included (color-coded reagents)
+FULL VALIDATION PACKAGE – assays are optimized for clinical samples
+ HIGH QUALITY GUARANTEED – results you can rely on
+ WIDELY CITED in 1500 + publications

Biomedica – Complete ready-to-use ELISA kits for superior performance and reproducibility

RELATED PRODUCTS

Osteoprotegerin (OPG) ELISA , soluble RANKL ELISA, Periostin ELISA, DKK-1 ELISA ,  Sclerostin ELISA

FGF23 ELISA , IL-6 ELISA  ,  VEGF ELISA ,  Angiopoietin-2 ELISA

MICRORNA  Analysis 

osteomiR^®– bone miRNA biomarkers highlights:

• Novel minimally invasive biomarkers to detect high imminent fracture-risk in osteoporosis
• 19 individual bone-related biomarkers with distinct information content

RELATED PUBLICATIONS

Novel biological markers of bone: from bone metabolism to bone physiology. Rheumatology (Oxford). Chapurlat RD, Confavreux CB. 2016; 55(10):1714-25.

Abstract

Biochemical markers of bone turnover have been used for decades in the management of bone diseases, to assess the prognosis of these conditions and to monitor treatments. The new markers, however, also reflect specific physiological mechanisms in the bone or other organs. Periostin may be more specific to the periosteum; cathepsin K is an osteoclastic enzyme that may be involved in the cardiovascular system and joints; Dickkopf-1 is involved in bone formation and vascular calcification; sclerostin is a major regulator of bone formation in response to mechanical loading and may also play a role in chronic kidney disease bone and mineral disorder; sphingosine-1-phosphate is a lipid mediator interacting with bone resorption. Some of the bone markers are in fact hormones produced by the bone that affect various physiological and pathological functions in other organs. Thus, osteocalcin is produced by osteoblasts and participates in the regulation of insulin sensitivity and fertility in men. Fibroblast growth factor 23 is produced by osteocytes to regulate phosphorus and 1,25(OH)2D3, but it also plays a major role in the adverse consequences of declining renal function, in particular with respect to the myocardium. Micro RNAs are single-stranded RNAs that regulate several pathways, including the development timing, organogenesis, cell apoptosis, proliferation and differentiation. Their serum concentration may reflect the links between bone physiology and certain conditions in other organs, for example, the cardiovascular system.

Bones have many important biological functions. Bone biomarkers have gained attention in clinical research for the assessment of bone-related diseases. Some of the biomarker proteins have been found to represent useful targets for therapeutic antibodies.

Biomarkers in Bone Biology

Function of the human skeleton

The human skeletal system gives the body it´s structure and helps to protect and support the internal organs. It forms a part of the muscular-skeletal systems that helps the body to move. Throughout our lifetime, the human skeleton undergoes constant remodeling. This dynamic process, degrading bone and replacing it with new tissue maintains bone mass. The continuous cycle of bone resorption and bone growth is also known as bone metabolism.

Bone remodeling

Bone remodeling is a tightly regulated process performed by hormones, cell-signaling molecules, and bone cells. These specific bone cells are osteoclasts, osteoblasts, and osteocytes. The cells are in constant communication with each other through secreted factors, such as osteoprotegerin, RANKL, and sclerostin. These regulatory systems keep the bone remodeling balanced. Imbalances in bone metabolism can lead to bone diseases.

Role of RANKL, RANK, and OPG in bone biology

 Bones are broken down by osteoclasts and rebuilt by osteoblasts.

RANKL receptor activator is a mediator of bone resorption and OPG acts as a decoy receptor.

 

Osteoprotegerin (OPG) is produced by osteoblasts, cells that synthesize bone. OPG is a decoy receptor and binds to RANKL, antagonizing its binding to RANK.

RANKL (receptor activator of nuclear factor kappa-B ligand) is secreted by osteoblasts and binds to the RANK receptor on osteoclast precursor and mature osteoclast cells. RANKL stimulates bone resorption.

 

Role of Sclerostin, FGF23, DKK-1, and Periostin in bone biology

 

 

Biomarkers in Bone Biology

 

Bone cells have been reported to have endocrine functions that affect multiple organs. The most abundant cell type in the bone are osteocytes residing within the bone matrix and comprising 90% to 95% of the bone cells. Osteocytes play a significant role in the regulation of osteogenesis, releasing osteocyte-related biomarkers such as sclerostin (SOST), fibroblast growth factor 23 (FGF23), and Dickkopf-1 (DKK-1).

Sclerostin (SOST) is mainly produced by osteocytes and is considered as the major regulator of bone formation. More recently, Sclerostin has been shown to stimulate the osteocyte synthesis of fibroblast growth factor-23, potentially contributing to the regulation of phosphate homeostasis.

Fibroblast growth factor 23 (FGF23) is a hormone that is mainly secreted by osteocytes and osteoblasts. It regulates phosphate and vitamin D levels and functions as a central endocrine hormone regulating phosphate balance.

Dickkopf-1 (DKK-1) is an extracellular protein. DKK-1 plays a role in the regulation of bone metabolism, as it inhibits the differentiation of osteoblasts.

Periostin (POSTN) is an extracellular matrix protein that is preferentially expressed in the periosteum, a membrane covering the outer surface of bones which is responsible for growth.  Periostin has functions in osteology, tissue repair, oncology, cardiovascular and respiratory diseases, and in a variety of  inflammatory settings (e.g. asthma).

BIOMEDICA OFFERS HIGH QUALITY ELISA KITS FOR BONE BIOMARKERS 

 

widely cited in over 1100 publications

kit validations follow international quality guidelines

 

Sclerostin ELISA (cat.no. BI-20492)

OPG ELISA (cat.no. BI-20403)

RANKL ELISA (cat.no. BI-20462)

FGF23 intact ELISA (cat.no. BI-20700)

FGF23 C-terminal ELISA (cat.no. BI-20702)

DKK-1 ELISA (cat.no. BI-20413)

PERIOSTIN ELISA (cat.no. BI-20433)

 

RELATED LITERATURE

A Review of the Potential Application of Osteocyte-Related Biomarkers, Fibroblast Growth Factor-23, Sclerostin, and Dickkopf-1 in Predicting Osteoporosis and Fractures. Ramli FF, Chin KY. Diagnostics (Basel). 2020 Mar 6;10(3):145. doi: 10.3390/diagnostics10030145. PMID: 32155909; PMCID: PMC7151094.

Sclerostin Directly Stimulates Osteocyte Synthesis of Fibroblast Growth Factor-23. Wijenayaka AR, Yang D, Ormsby RT, Bonewald LF, Atkins GJ. Calcif Tissue Int. 2021 Jul;109(1):66-76. doi: 10.1007/s00223-021-00823-6. Epub 2021 Feb 22. PMID: 33616712.

Biology of the RANKL-RANK-OPG System in Immunity, Bone, and Beyond. Front Immunol. Walsh MC, Choi Y.2014 Oct 20;5:511. doi: 10.3389/fimmu.2014.00511. PMID: 25368616; PMCID: PMC4202272.

The Osteocyte: New Insights. Robling AG, Bonewald LF. Annu Rev Physiol. 2020 Feb 10;82:485-506. doi: 10.1146/annurev-physiol-021119-034332. PMID: 32040934; PMCID: PMC8274561.

 

 

Breast Cancer – the most common cancer worldwide

Breast cancer (BC) is the most commonly occurring cancer in women and the most common cancer overall.  Although it is mostly found in women, it can affect men as well. Breast tissue in men can also become malignant. Though male BCs are rare and occur in 1% of all BCs, men are often diagnosed at a more advanced stage. The delay in seeking medical attention often results in late presentation and poor prognosis.

October is breast cancer month  – raising global awareness on risks, the importance of screenings, and the options of treatment.

 

Related links

• Breast cancer statistics
• What’s the difference? Male breast cancer and female breast cancer.

 

Further readings

• Understanding breast cancer as a global health concern.

Wilkinson L et al., Br J Radiol. 2022.  PMID: 34905391; PMCID. Full text

 

Abstract

Breast cancer is now the most commonly diagnosed cancer in the world. The most recent global cancer burden figures estimate that there were 2.26 million incident cases in 2020 and the disease is the leading cause of cancer mortality in women worldwide. The incidence is strongly correlated with human development, with a large rise in cases anticipated in regions of the world that are currently undergoing economic transformation. Survival, however, is far less favourable in less developed regions. There are a multitude of factors behind disparities in the global survival rates, including delays in diagnosis and lack of access to effective treatment. The World Health Organization’s new Global Breast Cancer Initiative was launched this year to address this urgent global health challenge. It aims to improve survival across the world through three pillars: health promotion, timely diagnosis, and comprehensive treatment and supportive care. 

• Global challenges and policy solutions in breast cancer control.

Trapani D et al.,  Cancer Treat Rev. 2022. PMID: 35074727.

 Cancer research

Prognostic exploratory biomarkers

Circulating biomarkers have the potential to provide valuable insight into disease progression. 

 

Discover Biomarker ELISA kits for cancer research – developed and manufactured by Biomedica

•  Neuropilin-1  

regulator of tumor biology – expressed by endothelial cells – isoform-specific receptors for VEGF – checkpoint target –  association with poor prognosis in BC patients.

• Periostin

extracellular matrix protein – novel therapeutic target –  marker of glioma malignancy and potential tumor recurrence – high serum levels associated with a poor survival in BC patients.

• Semaphorin 4D

glycoprotein – emerging clinical biomarker and therapeutic target in cancer – association with cancer progression and the bone metastases.

• Osteoprotegerin, RANKL

contribution to development of bone metastases an –in earlier stages of cancer influence on tumor biology.

• LRG1

Leucine-rich alpha-2-glycoprotein 1  – LRG1 – involved in pathogenic angiogenesis in cancer – wide spread in the microenvironment of numerous tumors – contributes to vascular dysfunction – potential therapeutic target.

• Angiopoietin-2

ANG2 – ANGPT2 – glycoprotein – drives vessel growth – immune target – involved in resistance to anti-VEGF therapy – possible predictive and prognostic biomarker for immune checkpoint therapy.

• IL-6

important cytokine during breast cancer progression – IL6 triggers activation of STAT2 in breast tumors – soluble factor IL6 could be used for early diagnosis of BC or prevent development of metastasis to the bone.  

• VEGF  

Vascular growth factor – potent cytokine that induces tumor angiogenesis – subtype VEGFA and VEGF Receptor -2 are therapeutical targets.

Further information on our products can be found on our website

International agency for research on cancer – WHO

Cancer research for the prevention and early recognition of cancer

Promoting cancer research to beat cancer: prevention and early detection of cancer is essential to control the disease. Understanding the causes of cancer and the ability to detect cancer sooner has a great impact on the survival and the outcome of patients.

Subsequently, early detection strategies and progress in diagnostic procedures will help to develop treatments to control the disease.

Promoting cancer research:

Exploring new biomarkers may help to identify the disease early.

Biomedica offers a range of novel biomarker ELISA kits for your cancer research.

Novel research biomarkers for cancer research include:  Periostin,  Neuropilin-1,  Semaphorin 4D

A range of cytokine ELISA kits complete  the panel:  Interleukin-6,  VEGF,  Angiopoietin-2 .

See our comprehensive “Oncology Biomarker Brochure “ for more information or contact us directly info@bmgrp.com .

We will be glad to meet you.

RELATED LITERATURE:

Promoting Cancer Early Diagnosis –  https://www.who.int

“Early diagnosis of cancer focuses on detecting symptomatic patients as early as possible so they have the best chance for successful treatment. When cancer care is delayed or inaccessible there is a lower chance of survival, greater problems associated with treatment and higher costs of care. Early diagnosis improves cancer outcomes by providing care at the earliest possible stage and is therefore an important public health strategy in all settings…”   Read more

Understanding mechanisms of cancer initiation and development supports the need for an implementation of primary and secondary cancer prevention.

Pelosi E, Castelli G, Testa U.Ann Ist Super Sanita. 2019 Oct-Dec;55(4):371-379. doi: 10.4415/ANN_19_04_11. PMID: 31850865.

Abstract

The burden of cancer is increasing worldwide, with a continuous rise of the annual total cases. Although mortality rates due to cancer are declining in developed countries, the total number of cancer deaths continues to rise due to the increase in the number of aged people. Three main causes of cancer have been described, represented by environmental factors, hereditary factors and random factors related to defects originated during cell replication. The frequency of cancers is very different for the various tissues and there is great debate on the extent of the specific contribution of environmental factors and random factors (due to “bad luck”) to cancer development. However, there is consensus that about 50% of all cases of cancer are related to environment and are preventable. Although a part of cancers is related to intrinsic mechanisms non preventable of genetic instability, it is evident that implementation of primary and secondary prevention measures is the only affordable strategy to meet from a medical and economic point of view the tremendous pressure created on healthcare structures by the increased cancer burden. It is time to bypass the paradox of disease prevention: celebrated in principle, resisted in practice.

Ovarian Cancer Biomarkers: Moving Forward in Early Detection

Bonifácio VDB. Adv Exp Med Biol. 2020;1219:355-363. doi: 10.1007/978-3-030-34025-4_18. PMID: 32130708.

Abstract

Ovarian cancer is a silent cancer which rate survival mainly relays in early stage detection. The discovery of reliable ovarian cancer biomarkers plays a crucial role in the disease management and strongly impact in patient’s prognosis and survival. Although having many limitations CA125 is a classical ovarian cancer biomarker, but current research using proteomic or metabolomic methodologies struggles to find alternative biomarkers, using non-invasive our relatively non-invasive sources such as urine, serum, plasma, tissue, ascites or exosomes. Metabolism and metabolites are key players in cancer biology and its importance in biomarkers discovery cannot be neglected. In this chapter we overview the state of art and the challenges facing the use and discovery of biomarkers and focus on ovarian cancer early detection.

 Keywords: Cancer biomarkers; Early detection; Metabolomics; Ovarian cancer; Proteomics; Urine biomarkers.

 

Developed & manufactured by Biomedica – Biomarkers for Cancer Research

The identification and validation of biomarkers in cancer is essential to improve our understanding of the disease. The emergence of novel cancer biomarkers continues to grow as scientists strive to find promising novel therapeutic targets and new prognostic and predictive markers to fight the disease.

Discover Biomedica Biomarker Assays for Cancer Research – we offer a range of unique biomarker ELISAs for your research.

Advantages of Biomedica ELISA kits

• RELIABLE – full validation package
• CONVENIENT – assay range optimized for clinical samples
• EASY – ready to use prediluted calibrators & controls
• LOW sample volumes
• TRUSTED – widely cited

High specificity – known target binding sites through mapping data
The unique specificity of the proprietary antibodies used in the Biomedica ELISA kits ensure that the assays only measure the analyte of interest.

Discover Biomedica´s Biomarker ELISA kits for cancer research
Neuropilin-1, Periostin, Semaphorin 4D, Osteoprotegerin, RANKL, LRG1, IL-6, VEGF, Angiopoietin-2 and other

Biomarkers for Cancer Research – Learn more about the markers

The transmembrane protein Neuropilin-1 (NRP1) regulates tumor biology and has been identified as a checkpoint target (1). High tissue NRP-1 levels are associated with a poor prognosis in breast cancer patients. In a recent study (2), German researchers have shown that circulating soluble NRP1 serum levels are an independent marker for poor prognosis in early breast cancer. Soluble Neuropilin-1 was quantified in serum with the highly specific NRP1 ELISA from Biomedica. Therapeutic areas of NRP1.

The secreted extracellular matrix protein Periostin has evolved as a novel therapeutic target and is a robust marker of glioma malignancy and potential tumor recurrence. It has also been implicated in the pathogenesis of breast cancer as high serum levels of periostin are associated with a poor survival in breast cancer patients (3). Periostin was quantified in serum with the well characterized Biomedica Periostin ELISA that has been published (4). Therapeutic areas of Periostin.

Semaphorin 4D (Sema4D) is a glycoprotein that is emerging as clinical biomarker and as therapeutic target in cancer. It has been associated with cancer progression and the occurrence of bone metastases (5, 6). Therapeutic areas of Sema4D.

Leucine-rich alpha-2-glycoprotein 1 (LRG1) is a protein that is an important factor involved in pathogenic angiogenesis in cancer. It is abundantly present in the microenvironment of many tumors contributing to vascular dysfunction and thus serving as a potential therapeutic target (7). Therapeutic areas of LRG 1.

The RANKL/RANK/OPG system contributes to the development of bone metastases and influences tumor biology in earlier stages of cancer (9). Dysregulation has been widely documented in the context of metastatic bone disease (10). The Biomedica OPG and RANKL ELISA kits have been widely used in the respective studies.

Literature
1. Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy. Chuckran CA et al., J Immunother Cancer. 2020. 8(2):e000967.
2. Soluble Neuropilin-1 is an independent marker of poor prognosis in early breast cancer. Rachner TD et al., J Cancer Res Clin Oncol. 2021. 147(8):2233-2238.
3. High serum levels of periostin are associated with a poor survival in breast cancer. Rachner TD et al., 2020. 180(2):515-524.
4. Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier E J Clin Lab Anal. 2018. 32(2):e22252.
5. Plasma levels of Semaphorin 4D are decreased by adjuvant tamoxifen but not aromatase inhibitor therapy in breast cancer patients. Göbel A J Bone Oncol. 2019. 4;16:100237.
6. Semaphorins as emerging clinical biomarkers and therapeutic targets in cancer. Mastrantonio R et al., Theranostics. 202. 15;11(7):3262-3277.
7. Leucine-rich alpha-2-glycoprotein 1 (LRG1) as a novel ADC target. Javaid F et al., RSC Chem Biol. 2021. 31;2(4):1206-1220.
8. RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives. Infante M J Exp Clin Cancer Res. 2019. 8;38(1):12.
9. Serum receptor activator of nuclear factor κB ligand (RANKL) levels predict biochemical recurrence in patients undergoing radical prostatectomy. Todenhöfer T, BJU Int. 2014. 113(1):152-9.
10. Prognostic Value of RANKL/OPG Serum Levels and Disseminated Tumor Cells in Nonmetastatic Breast Cancer. Rachner TD et al., Clin Cancer Res. 2019. 15;25(4):1369-1378.

 

Globally, about 1 in 6 deaths is related to cancer. Advances in cancer research have improved the prevention, the detection, and the treatment of cancer. Understanding on how cancers starts, grows and spreads is important for cancer treatment. Biomarkers play a critical role at all stages of the disease and serve as therapeutic targets (1).  

Biomarkers in Cancer Research

NEUROPILIN-1 is a checkpoint target

The biomarker Neuropilin-1 (NRP1) has gained renewed attention as it is implicated in promoting tumor progression. It acts as a co-receptor to VEGF (Vascular Endothelial Growth Factor) and induces angiogenesis, the process of the formation of new blood-vessels (2). NRP-1 is expressed in a variety of cancers including lung, prostate, pancreas or colon carcinoma. In metastatic melanoma, NRP-1 plays a crucial role in melanoma aggressiveness and evidence supports its use as a target for therapies (3) .

More recently, Neuropilin-1 has been identified as a checkpoint target with unique implications for cancer immunology and immunotherapy (4). This review discusses the increasing literature on Neuropilin-1 mediated immune modulation providing a rationale to categorize NRP1 as a key checkpoint in the tumor microenvironment (TME) as well as a promising immunotherapeutic target.

Did you know:  Neuropilin-1 can easily be detected in serum, plasma and in cell culture supernatants using a conventional ELISA kit?

The assay is fully validated for clinical use in human samples but also works in non-human samples. Only 10µl sample is required.

 For more information contact us   at BIOMEDICA

 Neuropilin-1 (NRP1) ELISA assay highlights:

-Highly specific using epitope mapped antibodies
-Detects free and ligand-bound soluble NRP1
-10 µl sample/well

  Literature:

1. Biomarkers and Its Application in Cancer Research. Jiancheng Hu and Qiang You. Biomark Applic 2017: 103. DOI: 10.29011/BMAP-103. 100103.
2. VEGF binding to NRP1 is essential for VEGF stimulation of endothelial cell migration, complex formation between NRP1 and VEGFR2, and signaling via FAK Tyr407 phosphorylation. Herzog B, Pellet-Many C, Britton G, Hartzoulakis B, Zachary IC. Mol Biol Cell. 2011 :;22(15):2766-76. doi: 10.1091/mbc.E09-12-1061. PMID: 21653826.
3. Neuropilin-1 as Therapeutic Target for Malignant Melanoma. Graziani G, Lacal PM. Front Oncol. 2015;5:125. Published 2015 Jun 3. doi:10.3389/fonc.2015.00125.
4. Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy. Chuckran CA, Liu C, Bruno TC, Workman CJ, Vignali DA. J Immunother Cancer. 2020 Jul;8(2):e000967. doi: 10.1136/jitc-2020-000967. PMID: 32675311; PMCID: PMC7368550:

Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy

Abstract

Checkpoint blockade immunotherapy established a new paradigm in cancer treatment: for certain patients curative treatment requires immune reinvigoration. Despite this monumental advance, only 20%-30% of patients achieve an objective response to standard of care immunotherapy, necessitating the consideration of alternative targets. Optimal strategies will not only stimulate CD8⁺ T cells, but concomitantly modulate immunosuppressive cells in the tumor microenvironment (TME), most notably regulatory T cells (T_reg cells). In this context, the immunoregulatory receptor Neuropilin-1 (NRP1) is garnering renewed attention as it reinforces intratumoral T_reg cell function amidst inflammation in the TME. Loss of NRP1 on T_reg cells in mouse models restores antitumor immunity without sacrificing peripheral tolerance. Enrichment of NRP1⁺ T_reg cells is observed in patients across multiple malignancies with cancer, both intratumorally and in peripheral sites. Thus, targeting NRP1 may safely undermine intratumoral T_reg cell fitness, permitting enhanced inflammatory responses with existing immunotherapies. Furthermore, NRP1 has been recently found to modulate tumor-specific CD8⁺ T cell responses. Emerging data suggest that NRP1 restricts CD8⁺ T cell reinvigoration in response to checkpoint inhibitors, and more importantly, acts as a barrier to the long-term durability of CD8⁺ T cell-mediated tumor immunosurveillance. These novel and distinct regulatory mechanisms present an exciting therapeutic opportunity. This review will discuss the growing literature on NRP1-mediated immune modulation which provides a strong rationale for categorizing NRP1 as both a key checkpoint in the TME as well as an immunotherapeutic target with promise either alone or in combination with current standard of care therapeutic regimens.

Keywords: immunomodulation; immunotherapy; tumor microenvironment.

Check out our biomarker ELISA kits for cancer research 

√  USER-FRIENDLY – ready to use calibrators & controls
√  RELIABLE – full validation package

-Neuropilin-1 – BI-20409
-Semaphorin 4D – BI-20405
-Periostin – BI-20433
-VEGF – BI-VEGF
-Angiopoietin-2 – BI-ANG2

 

Osteoporosis is a disease that weakens bone. When women get older, at the time around menopause, bone loss increases. Poor nutrition, lack of exercise, hormonal changes and other factors influence bone health. Early intervention can delay the development of osteoporosis and novel biomarkers may help to identify people at risk.

Bone Health & Osteoporosis – what women should know

BIOMEDICA offers Bone Biomarker ELISA Kits for clinical research

Complete ready to use kits – HIGH QUALITY GUARANTEED

Related products

Osteoprotegerin (OPG) ELISA  , DKK-1 ELISA ,  Sclerostin ELISA , soluble RANKL ELISA

IL-6 ELISA  , VEGF ELISA ,  Angiopoietin-2 ELISA

Bone Health & Osteoporosis – what women should know

Related publications

The effect of exercise intensity on bone in postmenopausal women (part 2): A meta-analysis.

Kistler-Fischbacher M, Weeks BK, Beck BR. Bone. 2021 Feb;143:115697. doi: 10.1016/j.bone.2020.115697. Epub 2020 Dec 24. PMID: 33357834.

Abstract

Background: Previous reviews have concluded that exercise has only modest effects on bone mineral density (BMD) in postmenopausal women. Despite the well-recognized strong positive relationship between load magnitude and bone response observed from animal research, the majority of human trials have examined the effects of only low to moderate intensity exercise on bone. We speculated that meta-analysing according to intensity may reveal a more potent exercise effect at higher intensity.

Objectives: To determine the effects of low, moderate and high intensity exercise on BMD at the spine and hip in postmenopausal women.

Methods: Electronic databases and reference lists were searched for RCTs that examined the effect of exercise compared to control on DXA-derived lumbar spine, femoral neck or total hip BMD in healthy postmenopausal women. Interventions were classified as low, moderate or high intensity and pooled based on classification. Mean differences (MD) were calculated using random effects models and a risk of bias analysis was undertaken. To determine the effect of different exercise types (resistance and impact training) on BMD outcomes, subgroup analyses for all intensity categories and outcomes were conducted. Separate meta-analyses were undertaken to examine the influence of adding exercise to a bone medication intervention and to examine exercise effects on fracture risk.

Results: Fifty-three trials, testing 63 interventions (19 low, 40 moderate, 4 high intensity) were included. At the lumbar spine, high intensity exercise yielded greater BMD effects (MD = 0.031 g/cm² 95% CI [0.012, 0.049], p = 0.002) than moderate (MD = 0.012 g/cm² 95% CI [0.008, 0.017], p < 0.001) and low intensity (MD = 0.010 g/cm² 95% CI [0.005, 0.015], p < 0.001). Low and moderate intensity exercise was equally effective at the femoral neck (low: 0.011 g/cm² 95% CI [0.006, 0.016], p < 0.001; moderate: 0.011 g/cm² 95% CI [0.007, 0.015], p < 0.001), but no effect of high-intensity exercise was observed. Moderate intensity exercise increased total hip BMD (0.008 g/cm² 95% CI [0.004, 0.012], p < 0.001), but low intensity did not. There were insufficient data to meta-analyse the effect of high intensity exercise at the total hip. Resistance training, potentially in combination with impact training, appears to be the most effective osteogenic stimulus at the spine and hip. Findings from meta-regression analyses were not informative and no influence of exercise on medication efficacy was observed. Risk of bias was mainly low or unclear due to insufficient information reported.

Conclusion: High intensity exercise is a more effective stimulus for lumbar spine BMD than low or moderate intensity, but not femoral neck BMD, however, the latter finding may be due to lack of power. While data from high-intensity exercise interventions are limited, the current comprehensive meta-analysis demonstrates the same positive relationship between load magnitude and bone response in humans that is observed in animal research. Findings have implications for optimal exercise prescription for osteoporosis in postmenopausal women.

Nutrition in the prevention and control of osteoporosis.

Ortega RM, Jiménez Ortega AI, Martínez García RM, Cuadrado Soto E, Aparicio A, López-Sobaler AM. Nutrición en la prevención y el control de la osteoporosis Nutr Hosp. 2021 Jan 13;37(Spec No2):63-66. Spanish. doi: 10.20960/nh.03360. PMID: 32993301.

Abstract

Objective: although osteoporosis develops in advanced stages of life, it must be prevented and stopped from the pediatric age, acting on modifiable factors, especially diet and lifestyle. The objective of this work is to review the latest evidence on nutritional improvements that can help in the prevention and control of the disease. Methods: bibliographic search related to the topic. Results: it is advisable to avoid energy restrictions, especially in postmenopausal women and particularly if they have osteopenia/osteoporosis since, in relation to these pathologies, excess weight may be preferable, rather than underweight. Protein intake higher than the recommended one is beneficial for the bone, provided that the calcium intake is adequate. Excessive intake of sugar and saturated fat should be avoided, but attempts should be made to achieve the nutritional goals set for ω-3 polyunsaturated fatty acids and fiber. It is important to monitor vitamin D status and calcium intake, which is inadequate in high percentages of individuals, as well as improving the contribution of vitamins K, C and group B, and also magnesium, potassium, iron, zinc, copper, fluorine, manganese, silicon and boron, and avoiding the excessive contribution of phosphorus and sodium. Conclusions: osteoporosis is an underdiagnosed pathology and of increasing prevalence. Due to its high morbidity and mortality, prevention is important and, from a nutritional point of view, it is convenient to bring the diet closer to the theoretical ideal. In general, increasing the consumption of dairy products, fish, vegetables and fruits, as well as reducing the consumption of salt, during childhood and throughout life, seems convenient for the bone improvement of most of the population.

Osteoporosis

Compston JE, McClung MR, Leslie WD. Lancet. 2019 Jan 26;393(10169):364-376. doi: 10.1016/S0140-6736(18)32112-3. PMID: 30696576.

 Abstract

Fractures resulting from osteoporosis become increasingly common in women after age 55 years and men after age 65 years, resulting in substantial bone-associated morbidities, and increased mortality and health-care costs. Research advances have led to a more accurate assessment of fracture risk and have increased the range of therapeutic options available to prevent fractures. Fracture risk algorithms that combine clinical risk factors and bone mineral density are now widely used in clinical practice to target high-risk individuals for treatment. The discovery of key pathways regulating bone resorption and formation has identified new approaches to treatment with distinctive mechanisms of action. Osteoporosis is a chronic condition and long-term, sometimes lifelong, management is required. In individuals at high risk of fracture, the benefit versus risk profile is likely to be favourable for up to 10 years of treatment with bisphosphonates or denosumab. In people at a very high or imminent risk of fracture, therapy with teriparatide or abaloparatide should be considered; however, since treatment duration with these drugs is restricted to 18-24 months, treatment should be continued with an antiresorptive drug. Individuals at high risk of fractures do not receive adequate treatment and strategies to address this treatment gap-eg, widespread implementation of Fracture Liaison Services and improvement of adherence to therapy-are important challenges for the future.

The Utility of Biomarkers in Osteoporosis Management.

Garnero P. Mol Diagn Ther. 2017 Aug;21(4):401-418. doi: 10.1007/s40291-017-0272-1. PMID: 28271451.

Abstract

The measurement of bone turnover markers is useful for the clinical investigation of patients with osteoporosis. Among the available biochemical markers, the measurements of serum procollagen type I N-terminal propeptide (PINP) and the crosslinked C-terminal telopeptide (serum CTX) have been recommended as reference markers of bone formation and bone resorption, respectively. The important sources of preanalytical and analytical variability have been identified for both markers, and precise measurement can now be obtained. Reference interval data for PINP and CTX have been generated across different geographical locations, which allows optimum clinical interpretation. However, conventional protein-based markers have some limitations, including a lack of specificity for bone tissue, and their inability to reflect osteocyte activity or periosteal metabolism. Thus, novel markers such as periostin, sclerostin and, sphingosine 1-phosphate have been developed to address some of these shortcomings. Recent studies suggest that the measurements of circulating microRNAs, a new class of marker, may represent early biological markers in osteoporosis. Bone markers have been shown to be a useful adjunct to bone mineral density for identifying postmenopausal women at high risk for fracture. Because levels of bone markers respond rapidly to both anabolic and anticatabolic drugs, they are very useful for investigating the mechanism of action of new therapies and, potentially, for predicting their efficacy to reduce fracture risk.