title: Elevated levels of Dickkopf-related protein 3 in seminal plasma of prostate cancer patients.
abstract: BACKGROUND
  Expression of Dkk-3, a secreted putative tumor suppressor, is altered in age-related proliferative disorders of the human prostate. We now investigated the suitability of Dkk-3 as a diagnostic biomarker for prostate cancer (PCa) in seminal plasma (SP).
  
  
  METHODS
  SP samples were obtained from 81 patients prior to TRUS-guided prostate biopsies on the basis of elevated serum prostate-specific antigen (PSA; > 4 ng/mL) levels and/or abnormal digital rectal examination. A sensitive indirect immunoenzymometric assay for Dkk-3 was developed and characterized in detail. SP Dkk-3 and PSA levels were determined and normalized to total SP protein. The diagnostic accuracies of single markers including serum PSA and multivariate models to discriminate patients with positive (N = 40) and negative (N = 41) biopsy findings were investigated.
  
  
  RESULTS
  Biopsy-confirmed PCa showed significantly higher SP Dkk-3 levels (100.9 ± 12.3 vs. 69.2 ± 9.4 fmol/mg; p = 0.026). Diagnostic accuracy (AUC) of SP Dkk-3 levels (0.633) was enhanced in multivariate models by including serum PSA (model A; AUC 0.658) or both, serum and SP PSA levels (model B; AUC 0.710). In a subpopulation with clinical follow-up > 3 years post-biopsy to ensure veracity of negative biopsy status (positive biopsy N = 21; negative biopsy N = 25) AUCs for SP Dkk-3, model A and B increased to 0.667, 0.724 and 0.777, respectively.
  
  
  CONCLUSIONS
  In multivariate models to detect PCa, inclusion of SP Dkk-3 levels, which were significantly elevated in biopsy-confirmed PCa patients, improved the diagnostic performance compared with serum PSA only.
authors.affiliation: Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria. christoph.zenzmaier@oeaw.ac.at
authors.forename: Christoph
authors.initials: C
authors.lastname: Zenzmaier
authors.forename: Martin
authors.initials: M
authors.lastname: Heitz
authors.forename: Helmut
authors.initials: H
authors.lastname: Klocker
authors.forename: Marion
authors.initials: M
authors.lastname: Buck
authors.forename: Robert A
authors.initials: RA
authors.lastname: Gardiner
authors.forename: Peter
authors.initials: P
authors.lastname: Berger
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D001681:Biological Assay; D018925:Chemokines; D015331:Cohort Studies; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D012372:ROC Curve; D012661:Semen / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins
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