Promoter methylation status of key genes and its implications in the pathogenesis of endometriosis, endometrioid carcinoma of ovary and endometrioid endometrial cancer.

Abstract

Epigenetic processes play an important role in various physiological processes as well as in the pathogenesis of many diseases. The role of altered DNA methylation in the pathogenesis of endometriosis and associated ovarian and endometrial cancers has not been explored in detail. Therefore, this study aimed to determine the promoter methylation status of genes involved in key biological processes in the pathogenesis of these three gynecological diseases. Tissue samples of endometriosis, endometrioid carcinoma of the ovary, endometrioid endometrial cancer, and control endometrium (n = 10 each) were obtained. DNA was extracted and subjected to bisulfite conversion using commercially available kits. The methylation status of COX2, VEGF, HIF1A, TNF, MYC, and TP53 genes was checked by methylation-specific PCR. The mRNA levels of MYC and TP53 were determined using qRT-PCR in all tissue samples. The promoter methylation status of COX2, VEGF, HIF1A, and TNF genes was significantly reduced in all three diseased study subjects (P < 0.05), whereas no significant difference was observed in the promoter methylation frequency of MYC and TP53 genes. Transcriptional expression of the MYC gene was significantly increased in all diseased groups (P < 0.001) whereas, transcriptional expression of the TP53 gene was significantly reduced in endometriosis and endometrioid carcinoma of the ovary and significantly increased in endometrioid endometrial cancer subjects compared to control subjects (P < 0.001). The findings suggest that the promoter regions of pro-inflammatory and pro-angiogenic genes involved in the common molecular pathophysiology of these three disorders were significantly hypomethylated and could be the reason for their over-expression associated with them. This indicates the role of epigenetics in the pathogenesis of these three diseases.