DOI: https://doi.org/10.26641/2307-5279.21.3.2017.149823

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

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

Abstract


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 strong 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.

Keywords


renal cell carcinoma; microRNA; biomarker; prognosis; survival

References


Федоренко З.П., Михайлович Ю.Й., Гулак Л.О. Рак в Україні, 2014–2015. / Бюл. нац. канцер-реєстру України №17. – Київ, 2015. – C. 56–57.

Pierorazio Phillip M., Michael H. et al. Management of Renal Masses and Localized Renal Cancer: Systematic Review and Meta-Analysis. // The Journal of Urology. – 2016 – V. 196, N 4. – P. 989–999.

Ljungberg B., Albiges L., Bensalah A. et al. EAU Guidelines on Renal Cell Carcinoma. European Association of Urology. – 2016. – Р. 17–20.

Keegan K.A. et al. Histopathology of surgically treated renal cell carcinoma: survival differences by subtype and stage // J. Urol. – 2012. – V. 188. – P. 391.

Leibovich B.C. et al. Histological subtype is an independent predictor of outcome for patients with renal cell carcinoma // J. Urol. – 2010. – V. 183. – P. 1309.

Wotschofsky Z., L. Gummlich, J. Liep, Carsten Stephan, ErginKilic, Klaus Jung, Jean-Noel Billaud, and Hellmuth-Alexander Meyer. Integrated microRNA and mRNA Signature Associated with the Transition from the Locally Confined to the Metastasized Clear Cell Renal Cell Carcinoma Exemplified by miR-146-5p // PloS One. – 2016. – V. 11, N 2.

Nofech-Mozes Roy, Heba W. Z. Khella, Andreas Scorilas, Leza Youssef, Sergey N. Krylov, EviLianidou, Konstantinos G. Sidiropoulos, Manal Gabril, Andrew Evans, and George M. Yousef. MicroRNA-194 Is a Marker for Good Prognosis in Clear Cell Renal Cell Carcinoma // Cancer Medicine. – 2016. – V. 5, N 4. – P. 656–664.

Samaan Sara, Heba W. Z. Khella, Andrew Girgis, Andreas Scorilas, EviLianidou, Manal Gabril, Sergey N. Krylov et al. miR-210 Is a Prognostic Marker in Clear Cell Renal Cell Carcinoma // The Journal of Molecular Diagnostics. – 2015. – N 2 . – P. 136–144.

Nakata Wataru, Motohide Uemura, Mototaka Sato, Kazutoshi Fujita, KentaroJingushi, Yuko Ueda, Kaori Kitae, KazutakeTsujikawa, and Norio Nonomura. Expression of miR-27a-3p Is an Independent Predictive Factor for Recurrence in Clear Cell Renal Cell Carcinoma // Oncotarget. – 2015. – N 25. – P. 21645–21654.

Terzuoli Erika, Sandra Donnini, Federica Finetti et al. Linking Microsomal Prostaglandin E Synthase-1/PGE-2 Pathway with miR-15a and -186 Expression: Novel Mechanism of VEGF Modulation in Prostate Cancer // Oncotarget. – 2016. – N 1. – P. 2–6.

Zhu Kang, Ying He, Cui Xia et al. MicroRNA-15a Inhibits Proliferation and Induces Apoptosis in CNE1 Nasopharyngeal Carcinoma Cells // Oncology Research. – 2016. – N 3(24). – P. 145–151.

Brandenstein Melanie, Jency J. Pandarakalam, Lukas Kroon et al. MicroRNA 15a, Inversely Correlated to PKCб, Is a Potential Marker to Differentiate between Benign and Malignant Renal Tumors in Biopsy and Urine Samples // The American Journal of Pathology. – 2012. – N. 5(180). – P. 1787–1797.