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Rachner, T.D.* ; Thiele, S.* ; Goebel, A.* ; Browne, A.* ; Fuessel, S.* ; Erdmann, K.* ; Wirth, M.P.* ; Froehner, M.* ; Todenhoefer, T.* ; Muders, M.H.* ; Kieslinger, M. ; Rauner, M.* ; Hofbauer, L.C.*

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

BMC Cancer 14:649 (2014)

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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.

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