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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.
Baseline Ang-2 plasma levels are an independent prognostic biomarker in refractory metastatic colorectal cancer
Chemorefractory is a term that is used to describe a cancer that does not respond to chemotherapy. Currently, no biomarkers are available to predict the efficacy of chemotherapy in chemorefractory metastatic colorectal cancer. Researchers from Italy have shown that circulating biomarker levels of Angiopoietin-2 (ANG2) increases early and predicts outcome with regorafenib but not with trifluridine/tipiracil treatment. Thus, baseline Ang-2 plasma levels are an independent prognostic biomarker in chemorefractory metastatic colorectal cancer. Read more: Early modulation of Angiopoietin-2 plasma levels predicts benefit from regorafenib in patients with metastatic colorectal cancer
Easy measurement of Angiopoietin-2 (ANG-2) in blood samples with only 20µl sample volume.
Check out the Biomedica ANGIOPOIETIN-2 (ANG2) ELISA kit
√ Full validation package – the assay is optimized for clinical samples
√ Kit includes ready to use standards and controls
√ HIGH QUALITY GUARANTEED
Related publications
Antoniotti C, Marmorino F, Boccaccino A, Martini S, Antista M, Rossini D, Zuco V, Prisciandaro M, Conca V, Zucchelli G, Borelli B, Cosentino P, Germani MM, Bosco MF, Carullo M, Vetere G, Moretto R, Giordano M, Masi G, Pietrantonio F, Zaffaroni N, Cremolini C. Eur J Cancer. 2022. 165:116-124. doi: 10.1016/j.ejca.2022.01.025. PMID: 35231767.
Abstract
Background: No biomarkers are currently available to predict the efficacy of trifluridine/tipiracil (FTD/TPI) in chemorefractory metastatic colorectal cancer. The multicohort REGOLAND study aims at exploring and validating circulating markers potentially able to predict benefit from regorafenib in this setting. Material and methods: In the retrospective ‘regorafenib exploratory cohort’, including 105 patients treated with regorafenib, baseline (d1) plasma levels of angiogenesis-related biomarkers and their early modulation after 15 days (d15) of treatment were investigated for correlation with clinical outcome. Based on a pre-specified statistical hypothesis, main retrospective findings were prospectively challenged in the ‘regorafenib validation cohort’, including 100 patients treated with regorafenib. Prospectively validated putative biomarkers were then assessed in the control ‘FTD/TPI cohort’, including 93 patients treated with FTD/TPI. Results: In the ‘regorafenib exploratory cohort’, the early (d15) increase of Angiopoietin-2 (Ang-2) was associated with longer progression-free survival (HR:0.57 [95%CI:0.38-0.88], P = 0.004) and a trend towards longer OS (HR:0.74 [95%CI:0.48-1.14], P = 0.165), than the early decrease. Similar results were prospectively confirmed in the ‘regorafenib validation cohort’ (HR for progression-free survival:0.72 [95%CI:0.48-1.08], P = 0.095; HR for OS:0.77 [95%CI:0.51-1.16], P = 0.204). No predictive impact was shown for the early modulation of Ang-2 in the ‘FTD/TPI cohort’. High baseline Ang-2 levels predict poor prognosis in all the investigated cohorts, independently of other clinical prognostic variables. Conclusions: The early modulation of circulating Ang-2 predicts the efficacy of regorafenib. Baseline Ang-2 plasma levels are an independent prognostic biomarker in chemorefractory metastatic colorectal cancer.
Angiopoietin-2 as a Prognostic Factor in Patients with Incurable Stage IV Colorectal Cancer.
Munakata S, Ueyama T, Ishihara H, Komiyama H, Tsukamoto R, Kawai M, Takahashi M, Kojima Y, Tomiki Y, Sakamoto K. J Gastrointest Cancer. 2021.52(1):237-242. PMID: 32166589.
Studies show that Angiopoietin-2 is a strong predictor in patients with SARS-CoV-2
Two research teams find that increased levels of the proinflammatory cytokine Angiopoietin-2 is crucial to predict transfer to the intensive care units and is responsible for hypercoagulation observed in critically ill patients infected with SARS-CoV-2.
Studies:
Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of … patients. Smadja DM et al., Angiogenesis, 2020;1-10. Full text
Elevated Angiopoietin-2 inhibits thrombomodulin-mediated anticoagulation in critically ill … patients. Hultstrom M et al., MedRxiv preprint server, 2021. Full text
SARS-CoV-2 infection has a diverse range of symptoms and may cause severe illness, in particular in patients with cardiovascular risk factors (1).
The infection is associated with an increase in procoagulant factors that have been shown to be associated with a higher mortality in patients with SARS-CoV-2 pneumonia (2). Pulmonary embolism and microvascular thrombosis in the lungs have been described in several reports in acute respiratory distress syndrome as well as in patients infected with SARS-CoV-2 (3).
Endothelial damage and inflammation in SARS-CoV-2 infection
The inflammatory cytokine storm occurring in patients infected with SARS-CoV-2, leads to the recruitment of leukocytes which damage the capillary endothelium. The disruption of the thromboprotective effect of endothelial cells likely leads to microvascular thrombosis. Thus, the endothelial damage and inflammation in several organs in patients with SARS-CoV-2 infection is a direct consequence of viral involvement and of the host inflammatory response (4).
Despite the routine thrombosis prophylaxis as standard of care treatment, the major complication in patients infected with SARS-CoV-2 is the hyperactivation of the coagulation system indicating a poor prognosis among these patients in intensive care (5).
Angiopoietin-2 (ANG2) is a soluble marker of endothelial activation
Angiopoietin-2 is a soluble protein that is involved in the regulation of vascular integrity, quiescence, and inflammation (6). ANG2 contributes to the formation of new vasculature. During angiogenesis, ANG2 exerts its effects via the angiopoietin-1/TIE2 receptor signaling system on endothelial cells. Disruption of this signaling leads to the loss of endothelial integrity. In consequence, the endothelium responds to various pro-inflammatory cytokines and growth factors.
Thus, Angiopoietin-2 is a soluble marker of endothelial activation and is involved in hemostasis, thrombo-inflammatory events or sepsis (7, 8).
ANG2 is a crucial factor to predict transfer to the intensive care unit
ANG2 induces inflammation and vascular hyperpermeability and correlates with adverse outcomes in several critical care syndromes (9). In patients infected with SARS-CoV-2, ANG2 was recently reported by Smadja and colleagues to be a relevant factor to predict transfer to the intensive care unit as it was associated with poor lung compliance (7). Thus, showing that endothelial activation reinforces the hypothesis of an infection-associated microvascular dysfunction.
Angiopoietin-2 inhibits anticoagulation in critically ill patients infected with SARS-CoV-2
Based on the above findings, Hulstrom and colleagues investigated if the highly elevated inflammatory cytokine ANG2 levels observed in SARS-CoV-2 patients had a direct effect on the coagulation system (10). Animal models and in vitro assays were included in their investigation. As thrombomodulin is expressed on the surface of endothelial cells where it binds thrombin and inhibits the intrinsic coagulation process, the scientists observed that ANG2 inhibits thrombomodulin-mediated anticoagulation and activation of protein C in human donor plasma. Furthermore, the increased ANG2 levels in patients infected with SARS-CoV-2 correlated with disease severity, hypercoagulation, and mortality by promoting hypercoagulation.
Revealing this novel mechanism for ANGPT2 in hypercoagulation the scientists suggest that inhibition of Angiopoietin-2 may be tested for treating severe cases of SARS-CoV-2 infection, as well as in certain other conditions, including sepsis (10).
Biomedica Angiopoietin-2 ELISA, Cat.No.BI-ANG2
Did you know?
Angiopoietin-2 (ANG-2) can reliably be measured by ELISA in human serum, plasma and urine samples with Biomedica’s fully validated assay kit. Only 20 µl of sample volume is required! The kit incorporates characterized epitope mapped antibodies and ready to use standards and controls. The assay range is optimized for clinical samples- no sample dilution required!
Features & Benefits
√ CONVENIENT – Assay range optimized for clinical samples;
– Ready to use standards and 2 controls included
√ RELIABLE – Rigorously validated according to FDA/EMEA/ICH guidelines
√ SPECIFIC – Characterized, epitope mapped capture and detection antibodies
√ QUALIFIED CUSTOMER SERVICE – supports you every step of the way
√ HIGH QUALITY GUARANTEED – https://www.bmgrp.com/quality
The Angiopoietin–2 ELISA kit was developed and manufactured by
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Literature:
- Clinical course and risk factors for mortality of adult inpatients with … in Wuhan, China: a retrospective cohort study. Zhou F et al., Lancet, 2020; 395(10229):1054-1062. https://pubmed.ncbi.nlm.nih.gov/32171076/ PMID: 32171076
- Abnormal Coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Tang N et al., J Thromb Haemost, 2020; 18(4): 844-847. https://pubmed.ncbi.nlm.nih.gov/32073213/ PMID: 32073213
- Pulmonary embolism in … patients: awareness of an increased prevalence. Poissy J et al, Circulation, 2020; 14; 142(2):184-186. https://pubmed.ncbi.nlm.nih.gov/32330083/ PMID: 32330083
- Endotheliitis in …. Varga S. Der Pathologe, 2020; 41(Suppl 2):99-102. https://pubmed.ncbi.nlm.nih.gov/33306138/ PMID: 33306138
- … and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Al-Samkari H et al., Blood, 2020:136, 489-500. https://pubmed.ncbi.nlm.nih.gov/32492712/ PMID: 32492712
- Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology. Akwii RG et al., Cells, 2019; 8(5): 471. https://pubmed.ncbi.nlm.nih.gov/31108880/ PMID: 31108880
- Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of … patients. Smadja DM et al., Angiogenesis, 2020;1-10. https://pubmed.ncbi.nlm.nih.gov/32458111/ PMID: 32458111
- Angiopoietin 2 levels in the risk stratification and mortality outcome prediction of sepsis-associated coagulopathy. Statz S et al., Clin Appl Thromb Hemost 24(8):1223–1233. https://pubmed.ncbi.nlm.nih.gov/29996658/ PMID: 29996658
- Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies. Li F et al., Therapeutic advances in respiratory disease, 2020; 14, 1753466620905274 (2020). https://pubmed.ncbi.nlm.nih.gov/32043429/ PMID: 32043429
- Elevated Angiopoietin-2 inhibits thrombomodulin-mediated anticoagulation in critically ill … patients. Hultstrom M et al., MedRxiv preprint server, 2021. https://www.medrxiv.org/content/10.1101/2021.01.13.21249429v1.full