Yu.O. Mytsyk, V.E. Dosenko, Yu.B. Borys, P.O. Illiuk, I.R. Maksymovych, N.V. Chernova

Application of microRNA-15a measured in tumor tissues as a prognostic biomarker of the renal cell carcinoma

Renal cell carcinoma (RCC) represents about 3 % of total oncologic pathology of adult population. The course of the disease and prognosis depends on many factors, among which anatomical, histological, clinical and molecular. At the moment neither of investigated molecular factors demonstrated sufficient accuracy in prediction of RCC biologic behavior and not recommended for use in clinical practice.

The aim of the study was to assess the potential for use microRNI-15a expression (miRNA), which was detected in tumor tissues as a prognostic biomarker of RCC.

The retrospective study included 64 patients with RCC after nephrectomy. For control 15 cases with healthy renal parenchymawere selected. Determination of miRNI-15a expression conducted after deparafinisation of blocks with tissuesamples with the following RNAisolation. MiRNAexpression was measuredusing reverse transcription and real-time polymerase chain reaction (PCR).

We achieved b statistic evidence (p<0.01) of difference in miR-15a expression values in RCC tissues and in healthy renal parenchyma:1,52±2,62 relative units (RU) vs 4,53E-03±3,11E-03 RU accordingly. In patients with RCC median of miRNA-15a expression was significantly higher than in patients without renal pathology: 0,10±2,62 RUvs 4,84E-03±3,11E-03 RU. Higher levels of miRNA-15a expression was associated with larger tumor size (Pearson correlation coefficient r=0,724), higher level of nuclear atypia, presence of necrosis and involvementof the regional lymph nodes. Relationship between level of miRNI-15a expression values and histological subtype of RCC wasn’t detected. In patients with RCC and with the level of miRNA-15a expression Ј0,10 RU 3-year and 5-year cancer-specific survival (CSS) were 100% and 97,0% accordingly, the average duration of survival was 59,88±0,12 months (95% CI - 59,66-60,11); 3-year and 5-year CSS in patients with expression >0,10 RU were 83,9% and 54,8% accordingly, the average duration of survival was 49,74±2,16 months (95% CI - 59,66-60,11).

Higher levels of microRNA-15a expression was associated with symptoms of more aggressive biological behavior of the disease, 5-year CSS in patients with RCC and with high levels of miRNA-15a expression was lower than in patients with a level of expression <0,10 RU (p<0,001).MiRNI-15a can be used as a prognostic biomarker of RCC.