[The hyper-methylated genes microRNA as potential markers of clear-cell carcinoma of kidney].

The clear-cell carcinoma of kidney is characterized by high rate of lethal outcomes. The lethality makes up to 16% in the first year after disease was diagnosed. The absence of efficient diagnostic at early stages (30% of all cases of clear-cell carcinoma of kidney are found out at late stages if there is metastatic disease) indicates the necessity of searching new biomarkers of clear-cell carcinoma of kidney. The disorders in methylation of regulatory genes of micro-RNA are one the causes of development of tumor. The purpose of the present study is to discover hyper-methylated genes of micro-RNA under clear-cell carcinoma of kidney and to evaluate their diagnostic and prognostic characteristics. The establishment of status of methylation of genes of micro-RNA in samples of DNA from tumor and unaltered tissue of 50 patients with clear-cell carcinoma of kidney was implemented using bisulfite conversion of DNA and subsequent methyl-specific polymerase chain reaction. The frequent hyper-methylation of seven genes of micro-RNA (miR-9-1/3, miR-124a-1/2/3, miR-34b/c, miR-129-2) in tumors of clear-cell carcinoma of kidney. Out of 7 analyzed genes of micro-RNA the systems of markers on 2-4 genes in each one were compiled. According ROC-analysis, the sensitivity of 4 markers systems reaches 88%, specificity - 94% (AUC 0.83-0.84). Furthermore, it is demonstrated that hyper-methylation of 5 genes of micro-RNA (miR-9-1/3, miR-124a-1/2/3, miR-34b/c, miR-129-2) is associated with parameters of progression of clear-cell carcinoma of kidney (stage, size of tumor, degree of differentiation, metastasis in lymph nodes on remote organs). Out of genes which hyper-methylation is associated with metastasis disease (miR-9-1/3, miR-124a-1/2/3, miR-34b/c, miR-129-2) 5 prognostic systems of markers were compiled and characterized. The hyper-methylation of gene miR-129-2 is a new efficient marker of prognosis of metastasis disease (sensitivity 75% and specificity 79%, AUC 0.77) that can be combined with markers discovered in other studies.