None of the currently investigated molecular markers demonstrated sufficient accuracy in prognostication of the renal cell carcinoma (RCC) oncologic outcomes; thus, none of them has been recommended for the application in the routine clinical practice. The role of miR-15a as a potential prognostic marker for RCC is still not unveiled. The aim of our study was to assess the expression of miR-15a in tumor tissues of the patients with RCC and to evaluate the possibility of its usage as a prognostic molecular biomarker of this disease. The retrospective included 64 adult patients with clear cell RCC (ccRCC) in whom radical or partial nephrectomy was conducted. After deparaffinization of formalin-fixed paraffin-embedded (FFPE) ccRCC specimens, the tissue expression of miR-15a was measured using the reverse transcription and quantitative polymerase chain reaction in the real time. For the reference, the expression of miR-15a was estimated in 15 FFPE tissue specimens of the normal renal parenchyma. Survival analysis involved all cases of non-metastatic RCCs (n = 57). Five-year cancer-specific survival (CSS) was estimated by means of the Kaplan-Meier method and was calculated from the date of surgery to the date of death. Patients with the RCC were characterized by significantly upregulated tumor tissue mean levels of miR-15a compared to the healthy controls: 0.10 ± 2.62 relative units (RU) versus 4.84E - 03 ± 3.11E - 03 RU (p < 0.001). Overexpression of miR-15a was strongly associated with poor histologic prognostic features of ccRCC. Poorly differentiated tumors tend to have more pronounced upregulation of miR-15a compared to highly differentiated lesions: Mean expression values were 4.57 ± 3.19 RU for Fuhrman grade 4 versus 0.02 ± 0.01 RU for Fuhrman grade 1 (p < 0.001). The metastatic involvement of the regional lymphatic nodules (N +) was associated with significantly upregulated miRNA-15a in comparison with N - cases: Mean expression values were 4.92 ± 2.80 RU versus 1.10 ± 2.29 RU, respectively (p < 0.001). In patients with miR-15a expression in RCC tissues ≤ 0.10 RU, mean 5-year CSS was significantly longer compared to patients with expression levels above this threshold: 92.31% (mean duration of survival-59.88 ± 0.12 months) versus 54.8% (mean duration of survival-49.74 ± 2.16 months), respectively (p < 0.001). The tissue expression of miR-15a could be used as a potential prognostic molecular biomarker for conventional RCC.

Clinical and experimental medicine. 2019 Aug 22 [Epub ahead of print]

Yulian Mytsyk, Yuriy Borys, Lesia Tumanovska, Dmytro Stroy, Askold Kucher, Katarina Gazdikova, Luis Rodrigo, Peter Kruzliak, Robert Prosecky, Peter Urdzik, Victor Dosenko

Department of Urology, Danylo Halytsky Lviv National Medical University, Pekarska str. 69, Lviv, Ukraine., General and Molecular Pathophysiology Department, Bogomoletz Institute of Physiology, National Academy of Sciences, Kiev, Ukraine., Department of Radiology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine., Department of Nutrition, Faculty of Nursing and Professional Health Studies, Slovak Medical University, Limbova 12, 833 03, Bratislava, Slovakia. ., Faculty of Medicine, University of Oviedo and Central University Hospital of Asturias (HUCA), Oviedo, Spain., Department of Internal Medicine, Brothers of Mercy Hospital, Polni 3, 63900, Brno, Czech Republic. ., Department of Internal Medicine, Brothers of Mercy Hospital, Polni 3, 63900, Brno, Czech Republic., Department of Gynaecology and Obstetrics, Faculty of Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Tr. SNP 1, 04001, Kosice, Slovakia. .