Kallikrein-Related Peptidase 4 Gene (KLK4) in Prostate Tumors: Quantitative Expression Analysis and Evaluation of Its Clinical Significance

BACKGROUND. Recently accumulating evidences underline the central role of the kallikrein-related peptidases family (KLKs) in prostate cancer (PCa) development and progression. The KLK4 is a prostate highly expressed gene under the transcriptional control of androgens, encoding for the KLK4 extracellular serine protease. The aim of this study is to investigate the expression status of KLK4 in PCa patients in order to reveal its utility in PCa establishment and clinical management. METHODS. Prostatic tissue specimens were obtained from 60 PCa and 59 benign prostate hyperplasia (BPH) randomly chosen patients. Using a developed quantitative real-time RTPCR method, KLK4 expression levels were determined in the specimens of the two patients' cohorts. Advance biostatistical analysis was completed to explore the clinical value of KLK4 expression in PCa and BPH patients. RESULTS. PCa patients presented a statistically significant (P = 0.002) elevation, more than threefold, of the KLK4 transcripts compared to BPH ones. The KLK4 expression levels were also positive correlated with PCa patients' stage (P = 0.031) and preoperative prostate-specific antigen (PSA) serum concentrations (P < 0.001). ROC curve and logistic regression analysis revealed the significant (P = 0.002) and the independent (P = 0.044) clinical value of the KLK4 expression for the discrimination of PCa from BPH patients. CONCLUSIONS. The KLK4 expression analysis reveals its up-regulation in PCa cells, which is significantly associated with the advanced stages of the disease and the patients' preoperative PSA serum levels. KLK4 quantification serves as an independent biomarker for the discrimination between the malignant and the benign nature of prostate tumors. Prostate 71: 1780-1789, 2011. (C) 2011 Wiley Periodicals, Inc.