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We studied the correlations between the levels of methylation of a group of 21 microRNA genes in 99 primary tumors and 29 macroscopic peritoneal metastases of ovarian cancer. Analysis of the level of methylation by quantitative methylation-specific PCR showed that co-methylation was detected for 13 pairs of microRNA genes in primary tumors and for 22 pairs in metastases. Pairs of microRNA genes that have shown significant co-methylation can be involved in common processes and pathways of gene regulation and interaction and can have common target genes. The results are highly significant and pairs of microRNA genes can be proposed as new potential markers for the diagnosis and prognosis of ovarian cancer metastasis. [ABSTRACT FROM AUTHOR]

The role of methylation in the regulation of genes of long noncoding RNA (lncRNA) is still poorly understood. We revealed new hypermethylated lncRNA genes in ovarian tumors and their effect on metastasis of ovarian cancer. A multiple and significant (p<0.001) increase in methylation of a group of lncRNA genes (MEG3, SEMA3B-AS1, ZNF667-AS1, and TINCR) was shown by quantitative methylation-specific PCR using the non-parametric Mann—Whitney test. Moreover, methylation of SEMA3B-AS1, ZNF667-AS1, and TINCR genes in ovarian cancer tumors was detected for the first time. Comparative analysis of 19 samples of peritoneal metastases and paired primary tumors showed a significant decrease in the methylation level of the same 4 genes: MEG3 (p=0.004), SEMA3B-AS1 (p=0.002), TINCR (p=0.002), and ZNF667-AS1 (p<0.001). Reduced methylation of suppressor lncRNA genes in peritoneal metastases is probably associated with the involvement of these lncRNA in the regulation of plastic reversion of the epithelial-mesenchymal transition to the mesenchymal-epithelial transition. Thus, the effect of lncRNA and their methylation on the development of tumors and metastases of ovarian cancer was demonstrated, which is important for understanding of the pathogenesis and mechanisms of metastasis of ovarian cancer. New properties of lncRNA can find application in the development of new approaches in the therapy of ovarian cancer. [ABSTRACT FROM AUTHOR]

We identified a group of miRNA genes whose methylation is associated with ovarian cancer metastasis. Based on these data, new markers and the systems of markers predicting tumor dissemination were selected. Using methylation-specific PCR and a representative set of 54 ovarian cancer samples, we identified 10 microRNA genes (MIR-124a-2, MIR-127, MIR-125b-1, MIR-129-2, MIR-137, MIR-193a, MIR-203a, MIR-34b/c, MIR-130b, and MIR-1258) whose methylation is associated with tumor metastasis. The greatest association was established for 4 genes: MIR-137, MIR-193a, MIR-34b/c, and MIR-130b (p<0.01). ROC analysis revealed 3 most optimal marker systems including 4-5 miRNA genes and characterized by high sensitivity (82-94%) and specificity (76-86%) at AUC=0.89-0.92. Methylation of any three genes from these systems is sufficient to predict metastasis with the specified accuracy. Detection of the group of hypermethylated miRNA genes with predictive value for ovarian cancer metastasis is of great importance for personalized treatment of the patients. [ABSTRACT FROM AUTHOR]

The study was designed to determine genes of microRNAs hypermethylated in malignant ovarian tumors and to select new diagnostic and prognostic markers of the disease and effective system of markers. Using methyl-specific PCR and a representative sample of 54 ovarian cancer specimens, we determined 5 microRNA genes (MIR-34b/c, MIR-9-1, MIR-124-3, MIR-129-2, and MIR-107) hypermethylated in the majority of tumor samples in comparison with paired samples of histologically unchanged tissue (48-57% vs. 4-19%, p<0.001). Using ROC-analysis, we selected an effective system of 4 markers for diagnosis of ovarian cancer (MIR-9-1, MIR-124-3, MIR-129-2, and MIR-107) characterized by high sensitivity and specificity (up to 87-94% at AUC=0.92) relative to the conventional norm (54 paired samples of histologically unchanged tissue) and absolute norm (18 ovarian tissue samples from subjects who died from non-tumor diseases). It was also shown that methylation of MIR-129-2, MIR-9-1, and MIR-34b/c genes is significantly (p<0.01) correlated with the clinical stage or the presence of metastases. The results indicate that epigenetic modifications of the studied microRNA genes are involved in the pathogenesis and progression of ovarian cancer and attest to their diagnostic and prognostic potential. [ABSTRACT FROM AUTHOR]

MicroRNA and methylation are important epigenetic mechanisms in the pathogenesis of cancer. The role of a group of microRNA hypermethylated genes in the pathogenesis of ovarian cancer was studied and their diagnostic and prognostic potential was evaluated. Studies on a representative sample of 54 ovarian cancer specimens with the use of methyl-specific PCR resulted in detection of five microRNA genes ( MIR-9-1, MIR-9-3, MIR-107, MIR-1258, and MIR-130b) methylated in the majority of tumor specimens in comparison with paired specimens of histologically intact tissue (37-57% vs. 4-9%, p<0.01). Methylation of three genes ( MIR-9-1, MIR-9-3, and MIR-130b) was significantly ( p≤0.05) associated with the parameters of ovarian cancer progress (clinical stage, differentiation degree, tumor size, and presence of metastases). These findings attest to oncosuppressive role of the studied microRNA genes ( MIR-9-1, MIR-9-3, MIR-107, MIR-1258, and MIR-130b) in the pathogenesis and progress of ovarian cancer and indicated their prognostic potential. [ABSTRACT FROM AUTHOR]