Quantified KLK15 gene expression levels discriminate prostate cancer from benign tumors and constitute a novel independent predictor of disease progression.

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.