Introduction/Background*Dickkopf-1 (DKK-1) is a secreted protein, known for suppressing the differentiation and activity of bone-building osteoblasts by acting as an inhibitor of Wnt-signalling. Soluble DKK-1 (sDKK-1) has been proposed as prognostic biomarker for a wide range of malignancies, however, clinical relevance of sDKK-1 as potential blood-based marker for ovarian cancer is unknown.

Methodology sDKK-1 levels were quantified in a cohort of 150 clinically documented ovarian cancer patients by a commercially available DKK-1 ELISA (Biomedica, Vienna, Austria).

Result(s)*Median sDKK-1 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 sDKK-1 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). sDKK-1 did not correlate with CA125, and higher sDKK-1 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 sDKK-1 was partly sustained in wtBRCA patients (PFS: HR = 0.507, 95%CI: 0.317 – 0.809; p = 0.004).

Conclusion*This is the first study demonstrating the prognostic relevance of sDKK-1 in ovarian cancer patients, including those with wtBRCA1/2 status. Our data encourage further evaluation of sDKK-1 in ovarian cancer patients, possibly in terms of a therapy monitoring marker or a response predictor for sDKK-1-directed targeted therapies.