Methylated genes as potential biomarkers in prostate cancer

Abstract

Prostate cancer is the most common malignancy of the urogenital tract. Although controversial, prostate-specific antigen (PSA) testing is widely used for screening and follow-up of prostate cancer, but because of its limited specificity and sensitivity, PSA is not an ideal test. We currently lack the necessary tools to differentiate between latent disease with little likelihood of clinical manifestation and aggressive tumours that are likely to metastasize and lead to potentially lethal disease. DNA methylation is an important epigenetic mechanism of gene regulation and plays essential roles in tumour initiation and progression. Currently, aberrant promoter hypermethylation has been investigated in specific genes from the following groups: tumour-suppressor genes, proto-oncogenes, genes involved in cell adhesion, and genes involved in cell-cycle regulation. Glutathione S-transferase P1 (GSTP1) has been shown to be a biomarker for prostate cancer. Other genes, e.g. CD44, PTGS2, E-cadherin, CDH13, and cyclin D2 have been found to be prognostic markers for prostate cancer. In cell samples derived from the urine, the presence of the hypermethylation of either GSTP1 or RASS1a has been shown to be both sensitive and specific for detecting prostate cancer. Several studies have found that analysis of hypermethylation using a panel of tumour-suppressor genes yielded better results for detecting prostate cancer than the analysis of single-gene methylation. Hence, these different panels (e.g. GSTP1, APC, PTGS2, T1G1 and EDNRB) are of interest for detecting prostate cancer. Also, the methylation profile of multiple regulatory genes might be altered at the time of cancer relapse. Thus, preliminary results on the use of the methylation status of specific genes as potential tumour biomarkers for the early diagnosis and the risk stratification of patients with prostate cancer are promising.