MicroRNA-15a tissue expression is a prognostic marker for survival in patients with clear cell renal cell carcinoma

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MYTSYK Yulian BORYS Yuriy TUMANOVSKA Lesia STROY Dmytro KUCHER Askold GAZDIKOVA Katarina RODRIGO Luis KRUŽLIAK Peter PROSECKY Robert URDZIK Peter DOSENKO Victor

Rok publikování 2019
Druh Článek v odborném periodiku
Časopis / Zdroj Clinical and Experimental Medicine
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www http://dx.doi.org/10.1007/s10238-019-00574-7
Doi http://dx.doi.org/10.1007/s10238-019-00574-7
Klíčová slova Cancer; Renal cell carcinoma; Clear cell; miRNA-15a; MicroRNA-15a; Biomarker; Genetic; Prediction; Prognosis; Survival
Popis 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.

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