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

BMC Cancer. 2014 Sep 2:14:649. doi: 10.1186/1471-2407-14-649.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood*
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / pathology
  • Survival Analysis
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins