title: High serum levels of Dickkopf-1 are associated with a poor prognosis in prostate cancer patients.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Endocrinology and Metabolic Bone Diseases, Department of Medicine III, TU Dresden, Fetscherstr 74, 01307 Dresden, Germany. tilman.rachner@uniklinikum-dresden.de.
authors.forename: Tilman D
authors.initials: TD
authors.lastname: Rachner
authors.forename: Stefanie
authors.initials: S
authors.lastname: Thiele
authors.forename: Andy
authors.initials: A
authors.lastname: Göbel
authors.forename: Andrew
authors.initials: A
authors.lastname: Browne
authors.forename: Susanne
authors.initials: S
authors.lastname: Fuessel
authors.forename: Kati
authors.initials: K
authors.lastname: Erdmann
authors.forename: Manfred P
authors.initials: MP
authors.lastname: Wirth
authors.forename: Michael
authors.initials: M
authors.lastname: Fröhner
authors.forename: Tilman
authors.initials: T
authors.lastname: Todenhöfer
authors.forename: Michael H
authors.initials: MH
authors.lastname: Muders
authors.forename: Matthias
authors.initials: M
authors.lastname: Kieslinger
authors.forename: Martina
authors.initials: M
authors.lastname: Rauner
authors.forename: Lorenz C
authors.initials: LC
authors.lastname: Hofbauer
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins