Evaluation of circulating Dickkopf-1 as a prognostic biomarker in ovarian cancer patients

Clin Chem Lab Med. 2021 Oct 25;60(1):109-117. doi: 10.1515/cclm-2021-0504. Print 2022 Jan 26.

Abstract

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.

Keywords: blood-based biomarker; ovarian cancer; prognosis; soluble Dickkopf-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ascites
  • Biomarkers, Tumor
  • CA-125 Antigen
  • Carcinoma, Ovarian Epithelial
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Ovarian Neoplasms* / metabolism
  • Peritoneal Neoplasms*
  • Prognosis

Substances

  • Biomarkers, Tumor
  • CA-125 Antigen
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins