Open Access Highly Accessed Research article

High serum levels of Dickkopf-1 are associated with a poor prognosis in prostate cancer patients

Tilman D Rachner1*, Stefanie Thiele1, Andy Göbel1, Andrew Browne1, Susanne Fuessel2, Kati Erdmann2, Manfred P Wirth2, Michael Fröhner2, Tilman Todenhöfer3, Michael H Muders4, Matthias Kieslinger5, Martina Rauner1 and Lorenz C Hofbauer16

Author Affiliations

1 Division of Endocrinology and Metabolic Bone Diseases, Department of Medicine III, TU Dresden, Fetscherstr 74, 01307 Dresden, Germany

2 Department of Urology, TU Dresden, Fetscherstr 74, 01307 Dresden, Germany

3 Department of Urology, University of Tübingen, Hoppe-Seyler-Straße 3, 72076 Tübingen, Germany

4 Institute of Pathology, TU Dresden, Fetscherstr 74, 01307 Dresden, Germany

5 Institute of Clinical Molecular Genetics and Tumor Genetics, Helmholtz Zentrum München, Marchioninistrasse 25, 81377 Munich, Germany

6 Center for Regenerative Therapies Dresden, TU Dresden, Fetscherstr 74, 01307 Dresden, Germany

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BMC Cancer 2014, 14:649  doi:10.1186/1471-2407-14-649

Published: 2 September 2014

Abstract

Background

The Wnt inhibitor Dickkopf-1 (DKK-1) has been linked to the progression of malignant bone disease by impairing osteoblast activity. In addition, there is increasing data to suggest direct tumor promoting effects of DKK-1. The prognostic role of DKK-1 expression in prostate cancer remains unclear.

Methods

A prostate cancer tissue microarray (n = 400) was stained for DKK-1 and DKK-1 serum levels were measured in 80 patients with prostate cancer. The independent prognostic value of DKK-1 expression was assessed using multivariate analyses.

Results

DKK-1 tissue expression was significantly increased in prostate cancer compared to benign disease, but was not correlated with survival. However, high DKK-1 serum levels at the time of the diagnosis were associated with a significantly shorter overall and disease-specific survival. Multivariate analyses defined high serum levels of DKK-1 as an independent prognostic marker in prostate cancer (HR 3.73; 95%CI 1.44-9.66, p = 0.007).

Conclusion

High DKK-1 serum levels are associated with a poor survival in patients with prostate cancer. In light of current clinical trials evaluating the efficacy of anti-DKK-1 antibody therapies in multiple myeloma and solid malignancies, the measurement of DKK-1 in prostate cancer may gain clinical relevance.

Keywords:
DKK-1; Prostate cancer; Prognosis