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

  • Daniel Martin Klotz ORCID logo , Theresa Link , Maren Goeckenjan , Pauline Wimberger , Anna R. Poetsch , Nikolai Jaschke , Lorenz C. Hofbauer , Andy Göbel , Tilman D. Rachner and Jan Dominik Kuhlmann ORCID logo EMAIL logo
Published/Copyright: October 25, 2021
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 60 Issue 1

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
Corresponding author: PD Dr. Jan Dominik Kuhlmann, 1Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 2German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany; 3National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; and Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany, E-mail:
Andy Göbel, Tilman D. Rachner and Jan Dominik Kuhlmann contributed equally to this work.

Funding source: Deutsche Forschungsgemeinschaft

Award Identifier / Grant number: GO 3055/1-1, HO 1875/24-1, 26-1, and 27-1, RA 2151/4-1 and 5-1

Funding source: Deutsche Krebshilfe

Award Identifier / Grant number: 70113573 and as part of the Mildred-Scheel Nachwuchszentrum

Acknowledgments

The authors would like to thank Babett Heschel for her excellent technical assistance.

  1. Research funding: The work was funded by the Deutsche Forschungsgemeinschaft to AG (GO 3055/1-1), LCH (HO 1875/24-1, 26-1, and 27-1) and to TDR (RA 2151/4-1 and 5-1) as part of the DFG Schwerpunktprogramm-2084 µBone as well as by the Deutsche Krebshilfe to AG and TDR (#70113573 and as part of the Mildred-Scheel Nachwuchszentrum).

  2. Author contributions: TDR, AG, DMK, JDK, PW and LCH made substantial contributions to the conception and design of the study. DMK, AG, JDK, TL, MG, NJ contributed to the experimental work or to the acquisition of clinical samples/data or to the analysis/interpretation of the results. JDK, AG and DMK, TL were involved in drafting the manuscript, creating figures or revising the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Written informed consent was obtained from all study participants and the study was approved by the Local Research Ethics Committee in Dresden (EK74032013).

  5. Ethical approval: The study was approved by the Local Research Ethics Committee in Dresden (EK74032013). All study methodologies conformed to the standards set by the Declaration of Helsinki.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2021-0504).

Received: 2021-04-27
Accepted: 2021-10-01
Published Online: 2021-10-25
Published in Print: 2022-01-26

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2021-0504
Keywords for this article
blood-based biomarker; ovarian cancer; prognosis; soluble Dickkopf-1

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. EU health policy is on the brink of a spectacular own-goal that will harm patients and hamper innovation
  4. Theranos revisited: the trial and lessons learned
  5. Reviews
  6. Review and evolution of guidelines for diagnosis of COVID-19 vaccine induced thrombotic thrombocytopenia (VITT)
  7. High-sensitivity cardiac troponins in pediatric population
  8. Opinion Papers
  9. Implementation of the new EU IVD regulation – urgent initiatives are needed to avert impending crisis
  10. Exploration of novel biomarkers for hypertensive disorders of pregnancy by comprehensive analysis of peptide fragments in blood: their potential and technologies supporting quantification
  11. General Clinical Chemistry and Laboratory Medicine
  12. Total lab automation: sample stability of clinical chemistry parameters in an automated storage and retrieval module
  13. Instability of corticotropin during long-term storage – myth or reality?
  14. External quality assessment of serum indices: Spanish SEQC-ML program
  15. Comparison of two LC-MS/MS methods for the quantification of 24,25-dihydroxyvitamin D3 in patients and external quality assurance samples
  16. Isotope dilution LC-MS/MS quantification of the cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor, lumacaftor, tezacaftor, elexacaftor, and their major metabolites in human serum
  17. Hematology and Coagulation
  18. The development of autoverification system of lymphocyte subset assays on the flow cytometry platform
  19. Cancer Diagnostics
  20. Comparison of the QuikRead go® point-of-care faecal immunochemical test for haemoglobin with the FOB Gold Wide® laboratory analyser to diagnose colorectal cancer in symptomatic patients
  21. Evaluation of circulating Dickkopf-1 as a prognostic biomarker in ovarian cancer patients
  22. Cardiovascular Diseases
  23. Soluble CD40 ligand and outcome in patients with coronary artery disease undergoing percutaneous coronary intervention
  24. Diabetes
  25. Lot variation and inter-device differences contribute to poor analytical performance of the DCA Vantage™ HbA1c POCT instrument in a true clinical setting
  26. Infectious Diseases
  27. Lipase elevation in serum of COVID-19 patients: frequency, extent of increase and clinical value
  28. Acknowledgment
  29. Acknowledgment
  30. Letters to the Editors
  31. Presepsin value predicts the risk of developing severe/critical COVID-19 illness: results of a pooled analysis
  32. Measuring accuracy of the neutralizing activity of COVID-19 convalescent plasma
  33. Evaluation of reference intervals for classical and alternative pathway functional complement assays
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  35. Cerebrospinal fluid neurogranin in Alzheimer’s disease studies: are immunoassay results interchangeable?
  36. Pepsin pretreatment corrects underestimation of 25-hydroxyvitamin D measurement by an automated immunoassay in subjects with high vitamin D binding protein levels
  37. A conspicuous reduced plasma creatinine: the first presenting sign of Waldenstrom macroglobulinemia
  38. Effect of non-linearity on rheumatoid factor assay in Beckman system IMMAGE800
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