HYPERMETHYLATION OF GLUTATIONE-S-TRANSFERASI (GSTP1) AS PLASMATIC MOLECULAR BIOMARKER FOR PROSTATE CANCER

Background: Currently, a widely used marker for the diagnosis and follow-up of Prostate cancer ( PC) is the Prostate Specific Antigen (PSA). Furthermore, in order to ensure an efficient monitoring of the patients at risk of PC, there is a growing need of new tools able to early identify these subject. Molecular analysis of neoplastic prostate tissues shown the inactivation of the Glutatione-S-Transferase gene (GSTP1), due to the hypermethylation. This features could be a potential biomarker for PC. The aim of this study is the specific and sensitive detection of the methylation status of GSTP1 gene in plasma. Methods: The methylation status of 5' promoter region of GSTP1 gene was obtained by methylation Sensitivity-PCR (MS-PCR). The test was optimaized in terms of the specificity, sensitivity. The diagnostic efficacy of the test was tested on the DNA from 20 healthy donors, 57 benign prostatic hypertrophy (BPH), and 57 PC patients. Results: GSTP1 promoter gene hypermethylation was detected in 0% of healthy subjects (20/20, median age 32.7 years), in 43.9% of patients with BPH (25/57 mean age 60.5 years) and in 57.6% of patients with PC (34/57 mean age 67.8 years). Significantly, the 81.8% of patients with PC, age > 65 years and total PSA <= 4 ng/ml were positive for the hyper-methylation status of GSTP1 gene. Conclusions: By this means, specific evaluation of methylation status of GSTP1 gene may be an useful tool for the prediction of patients at risk of PC. In addition the test is cost-effectiveness and could be used extensively for cancer prevention.