OVARIAN CANCER & DKK-1 a blood-based biomarker
Ovarian cancer is one of the most common types of cancer in women. Dickkopf-related protein 1 is a secreted protein postulated as a promising target for cancer immunotherapy. In this first study, researchers investigated the prognostic relevance of blood-based circulating soluble DKK-1 (sDKK-1) in ovarian cancer patients including those with wtBRCA 1/2 status. The data encourage further evaluation of sDKK1 in ovarian cancer patients, possibly in terms of a therapy monitoring marker or a response predictor for sDKK1-directed targeted therapies.
Learn more: Evaluation of circulating Dickkopf-1 as a prognostic biomarker in ovarian cancer patients. Klotz DM, Link T, Goeckenjan M, Wimberger P, Poetsch AR, Jaschke N, Hofbauer LC, Göbel A, Rachner TD, Kuhlmann JD. Clin Chem Lab Med. 2021 Oct 25. doi: 10.1515/cclm-2021-0504. Epub ahead of print. PMID: 34687595.
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Objectives: Dickkopf-1 (DKK1) is a secreted protein, known for suppressing the differentiation and activity of bone-building osteoblasts by acting as an inhibitor of Wnt-signalling. Soluble DKK1 (sDKK1) has been proposed as prognostic biomarker for a wide range of malignancies, however, clinical relevance of sDKK1 as potential blood-based marker for ovarian cancer is unknown.
Methods: sDKK1 levels were quantified in a cohort of 150 clinically documented ovarian cancer patients by a commercially available DKK1 ELISA (Biomedica, Vienna, Austria).
Results: Median sDKK1 level was significantly elevated at primary diagnosis of ovarian cancer compared to healthy controls (estimated difference (ED) of 7.75 ng/mL (95% CI: 3.01-12.30 ng/mL, p=0.001)). Higher levels of sDKK1 at diagnosis indicated an increased volume of intraoperative malignant ascites (ED 7.08 pmol/L, 95% CI: 1.46-13.05, p=0.02) and predicted suboptimal debulking surgery (ED 6.88 pmol/L, 95% CI: 1.73-11.87, p=0.01). sDKK1 did not correlate with CA125 and higher sDKK1 levels predicted a higher risk of recurrence and poor survival (PFS: HR=0.507, 95% CI: 0.317-0.809; p=0.004; OS: HR=0.561, 95% CI: 0.320-0.986; p=0.044). Prognostic relevance of sDKK1 was partly sustained in wtBRCA patients (PFS: HR=0.507, 95% CI: 0.317-0.809; p=0.004).
Conclusions: This is the first study demonstrating the prognostic relevance of sDKK1 in ovarian cancer patients, including those with wtBRCA 1/2 status. Our data encourage further evaluation of sDKK1 in ovarian cancer patients, possibly in terms of a therapy monitoring marker or a response predictor for sDKK1-directed targeted therapies.
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