Elevated levels of Dickkopf-related protein 3 in seminal plasma of prostate cancer patients

• Published in: Journal of translational medicine Vol. 9; no. 1; p. 193
• Main Authors: Zenzmaier, Christoph, Heitz, Martin, Klocker, Helmut, Buck, Marion, Gardiner, Robert A, Berger, Peter
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10.11.2011; BioMed Central; BMC
• Subjects: Aged; Biological Assay; Biomarkers; Biopsy; Cohort Studies; Colleges & universities; Competition; Development and progression; Dickkopf-3; Dkk-3; Gene expression; Genetic aspects; Humans; IEMA; Intercellular Signaling Peptides and Proteins - metabolism; Logistic Models; Male; Middle Aged; Multivariate Analysis; Physiological aspects; Polyclonal antibodies; Predictive Value of Tests; Prostate cancer; prostate-specific antigen; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - metabolism; Proteins; ROC Curve; Semen - metabolism; seminal fluid; Tumor proteins; Tumor suppressor genes; Validation studies; Austria
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/1479-5876-9-193

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). 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. 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. 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.