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Clinical features of the microRNA genes methylation in borderline ovarian tumors and depending on the histological structure in ovarian malignancies

Background: Borderline ovarian tumors (BOT) belong to the intermediate type between benign and malignant ovarian neoplasms. Serous borderline tumors share common molecular and genetic characteristics with serous carcinomas. An increase in the methylation level of microRNA (miRNA) genes group has been previously shown during the development and progression of ovarian cancer. However, the study results are contradictory, and their number is not sufficient for a consensus. Current study is the first to search for aberrant methylated genes of the BOT-specific microRNA and for some histological subtypes of ovarian cancer. 
Materials and methods: The study was based on a set of 99 paired (tumor/healthy) ovarian tumor samples. Methylation analysis was carried out with quantitative methyl-specific polymerase chain reaction (PCR). Screening for BOT biomarkers was performed in 21 genes of miRNA. 
Results: We have found that some miRNA genes (MIR124-1, MIR125B-1, MIR129-2, MIR132, MIR148A, MIR193A, MIR203A, MIR107, MIR1258, MIR339) were characterized by a high methylation level in the patients with BOT, compared to that in the tissues of healthy women. At the same time, the methylation level in the patients with malignant ovarian tumors (MOT) either differed slightly or was even lower. For the MIR129-2, MIR132, MIR148A, MIR203, MIR107 and MIR1258 genes, a higher level of methylation was detected in the BOT patients, compared to the MOT patients. The methylation level of the MIR148A gene in the BOT patients was 4-fold higher than that in the MOT (31.3% vs 7.9%, p = 0.047, multiple two-sided Kruskal-Wallis test). The methylation levels of the miRNA genes MIR148A and MIR191 were significantly reduced in serous cystadenocarcinoma and increased in serous and endometrioid adenocarcinomas. 
Conclusion: Methylation of the miRNA MIR148A and MIR191 genes is significantly associated with various histological variants of ovarian cancer. We have shown an increased methylation level of a number of miRNA genes in BOT, compared to MOT. In general, epigenetic factors play a role in the clinical differences between histological forms of ovarian cancer and borderline tumors.