Evaluation of possible association between endometriosis and Endometrioid carcinoma of ovary at epigenetic level

Abstract

Endometriosis, a chronic benign disease can lead to endometrioid carcinoma of ovary. Both diseases share several risk factors and molecular pathogenesis. In the present study, we tried to uncover the epigenetic association between the two. Tissue and blood samples of women with endometriosis (Ia), endometrioid carcinoma of ovary (Ib) and normal endometrium (II) were obtained from 30 subjects (n=10 each) after obtaining ethical clearance and informed consent. microRNA profiling was done in representative sample from each group by NGS (Illumina). Validation of eight selected miRNAs was done by qRT-PCR in all the samples along with selected target genes (COX 2, VEGF, HIF1A, TNF, MYC and TP53). Around 470 miRNAs (Group-Ia) and 572 miRNAs (Group-Ib) were differentially expressed with reference to Group-II as per NGS. Among these, expression of miR-449a, miR-34b, miR-16 and miR-20a were downregulated (Plt0.001) whereas, miR-99b, miR-125a, miR-143 and miR-145 were upregualted (Plt0.001) in both Group-Ia and Ib subjects. Except TP53, an augmented expression of study genes was observed in Group-I subjects. Leaving apart MYC and TP53, promoter methylation frequencies of study genes were significantly decreased in Group-I compared to Group-II as observed by methylation specific PCR. Lastly, serum miRNAs were evaluated by ROC curve analysis and except miR-20a, studied miRNAs displayed great diagnostic potential for endometriosis and only miR-125a for Group-Ib. Besides, they were able to discriminate endometriosis from endometrioid carcinoma of ovary. Concludingly, differential miRNAs and aberrant promoter methylation are vital in the pathogenesis of both diseases and certain studied miRNAs can serve potential biomarkers. newline