25P - Relationship between aberrant methylation of CpG islands of microRNA gene promoters and changes in their expression in epithelial ovarian cancer

Background

Epithelial ovarian cancer (EOC) is a disease found mainly in advanced stages and difficult to treat. The study of the expression and methylation of miRNA genes can become the basis for the development of potential new diagnostic and prognostic markers of EOC, as well as the basis for the development of targeted anticancer therapy.

Methods

80 paired samples of EOC (ovarian serous adenocracinoma) were obtained from the National Medical Research Center of Oncology named after N.N. Blokhin. MicroRNA expression was assessed by TaqMan-qPCR with kits from Applied Biosystems, USA. Analysis of methylation of promoter CpG islands of microRNA genes was carried out using bisulfite conversion followed by methyl-specific PCR.

Results

The methylation frequency in the tumor was higher than in paired norm for 10 microRNA genes (MIR-124-1, -124-2, -124-3, -125B-1, -127, -129-2, -132, -137, -193A and -339; p ≤ 5×10-4). ROC analysis showed that a combination of 4 microRNA genes (MIR-124-2, -127, -129-2, -137) can be proposed as a panel of EOC detection markers with sensitivity (Sn) 80%, specificity (Sp) 82 %, AUC=0.86. The combination of miRNA genes (MIR-193A, -129-2, -137) was characterized by Sn=90%, Sp=75% and AUC=0.90. For 5 out of 12 microRNAs studied, a high frequency of reduced expression was observed: miR-125b-5p - in 59% of tumor samples compairing to paired norms, miR-129-5p - in 55%, miR-132-3p - in 55%, miR-137 - in 52% , and miR-193a-5p in 66% (p ≤ 0.05). The correlation of changes in the expression of 12 microRNAs (miR-124-3p, -125b-5p, -127-5p, 129-5p, -132-3p, -137, -148a-3p, -191-5p, -193a-5p, -203a, -339-3p and -375) and changes in methylation of the genes encoding them rs=0.67-0.97 (according to Spearman), p ≤ 10-4.

Conclusions

The role of methylation in the regulation of the expression of 12 microRNAs and the association of the methylation status of 10 microRNA genes with EOC metastasis were revealed. 5 microRNAs downregulated by hypermethylation may find use as potential targets for EOC therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The state task FGFU-2022-0007 of the Ministry of Science and Higher Education of the Russian Federation.

Disclosure

All authors have declared no conflicts of interest.