Assessment of Glutathione-S-Transferase (GSTP1) methylation status is a reliable molecular biomarker for early diagnosis of prostatic intraepithelial neoplasia

Abstract

OBJECTIVE: Prostate Specific Antigen (PSA) is a commonly used marker for the diagnosis and follow-up of Prostate Cancer (PC) and Prostatic Intraepithelial Neoplasia (PIN). Furthermore, in order to ensure early detection of the patients at risk of PC and PIN, there is a growing need for new tools able to early identify this subject. Molecular analysis of neoplastic prostate tissues showed the inactivation of the Glutathione-S-Transferase gene (GSTP1) due to the hypermethylation. The aim of this study is the validation of the specific and sensitive detection of the methylation status of the GSTP1 gene for potential biomarker to assess early detection of PIN. PATIENTS AND METHODS: The methylation status of 5’ promoter region of the GSTP1 gene was obtained by Methylation Sensitivity-PCR (MS-PCR). The test was optimized in terms of the specificity and sensitivity. The cost-efficacy of the test was tested on the DNA from 20 donors healthy subject, 57 benign prostatic hypertrophy (BPH), and 57 PC patients. RESULTS: GSTP1 promoter gene methylation 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 methylation status of GSTP1 gene. CONCLUSIONS: In this way, specific evaluation of the methylation status of the GSTP1 gene may be a 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.

Keywords

• methylation sensitivity
• analytical validations
• molecular diagnostics
• gstp1
• prostate cancer