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

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 rel...

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Main Authors: Klotz, Daniel Martin (Author) , Link, Theresa (Author) , Goeckenjan, Maren (Author) , Wimberger, Pauline (Author) , Poetsch, Anna R. (Author) , Jaschke, Nikolai (Author) , Hofbauer, Lorenz C. (Author) , Göbel, Andy (Author) , Rachner, Tilman Daniel (Author) , Kuhlmann, Jan Dominik (Author)
Format: Article (Journal)
Language:English
Published: 2022
In: Clinical chemistry and laboratory medicine
Year: 2022, Volume: 60, Issue: 1, Pages: 109-117
ISSN:1437-4331
DOI:10.1515/cclm-2021-0504
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1515/cclm-2021-0504
Verlag, lizenzpflichtig, Volltext: https://www.degruyterbrill.com/document/doi/10.1515/cclm-2021-0504/html
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Author Notes:Daniel Martin Klotz, Theresa Link, Maren Goeckenjan, Pauline Wimberger, Anna R. Poetsch, Nikolai Jaschke, Lorenz C. Hofbauer, Andy Göbel, Tilman D. Rachner, Jan Dominik Kuhlmann
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Summary: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 wt BRCA 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 wt BRCA 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.
Item Description:Veröffentlicht von De Gruyter 25. Oktober 2021
Gesehen am 07.01.2022
Physical Description:Online Resource
ISSN:1437-4331
DOI:10.1515/cclm-2021-0504

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