title: Quantified KLK15 gene expression levels discriminate prostate cancer from benign tumors and constitute a novel independent predictor of disease progression.
abstract: BACKGROUND
  Several transcript variants of the kallikrein-related peptidase 15 gene (KLK15) have been identified up to now. The classical KLK15 mRNA isoform encodes for a non-truncated, functional protein. Aberrant KLK15 expression is found in breast, ovarian, and prostate cancers. Our aim in this present study was the specific quantitative expression analysis of the classical KLK15 mRNA transcript in prostate tumors and the examination of its clinical significance in prostate cancer.
  
  
  METHODS
  We isolated total RNA from 150 prostate tissue specimens and, following cDNA synthesis, the expression of KLK15 classical mRNA transcript was measured via quantitative Real-Time PCR using the TaqMan® chemistry. HPRT1 was used as a reference gene, and the absolute quantification approach, through the incorporation of standard curves, was applied for the calculation of normalized KLK15 expression.
  
  
  RESULTS
  KLK15 expression levels were significantly upregulated in malignant compared to benign samples (P < 0.001). The discriminatory value of KLK15 was confirmed by ROC curve and logistic regression analysis (both P < 0.001). KLK15 was also associated with advanced pathological stage (P = 0.023). KLK15-positive prostate cancer patients presented significantly shorter progression-free survival intervals, determined by biochemical relapse (P = 0.006), compared to KLK15-negative ones. Multivariate Cox regression analysis revealed that KLK15 expression is an independent predictor of biochemical recurrence (HR = 3.36, P = 0.038).
  
  
  CONCLUSIONS
  The present study unravels the important role of quantified KLK15 classical mRNA expression levels as a novel biomarker helpful for the differential diagnosis and prognosis of prostate cancer patients.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mavridis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stravodimos
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D003937:Diagnosis, Differential; D018450:Disease Progression; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C501608:KLK15 protein, human; D007610:Kallikreins