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

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Abstract

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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Funding

This study was supported by the Scientific Grant Agency of the Ministry of Education of the Slovak Republic under the contract no. Grant VEGA 1/0873/18.

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Authors and Affiliations

  1. Department of Urology, Danylo Halytsky Lviv National Medical University, Pekarska str. 69, Lviv, Ukraine

    Yulian Mytsyk & Yuriy Borys

  2. General and Molecular Pathophysiology Department, Bogomoletz Institute of Physiology, National Academy of Sciences, Kiev, Ukraine

    Lesia Tumanovska, Dmytro Stroy & Victor Dosenko

  3. Department of Radiology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine

    Askold Kucher

  4. Department of Nutrition, Faculty of Nursing and Professional Health Studies, Slovak Medical University, Limbova 12, 833 03, Bratislava, Slovakia

    Katarina Gazdikova

  5. Department of General Medicine, Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia

    Katarina Gazdikova

  6. Faculty of Medicine, University of Oviedo and Central University Hospital of Asturias (HUCA), Oviedo, Spain

    Luis Rodrigo

  7. Department of Internal Medicine, Brothers of Mercy Hospital, Polni 3, 63900, Brno, Czech Republic

    Peter Kruzliak & Robert Prosecky

  8. 2nd Department of Surgery, Faculty of Medicine, Masaryk University and St. Anne’s University Hospital, Brno, Czech Republic

    Peter Kruzliak

  9. Department of Gynaecology and Obstetrics, Faculty of Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Tr. SNP 1, 04001, Kosice, Slovakia

    Peter Urdzik

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  1. Yulian Mytsyk
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Correspondence to Katarina Gazdikova, Peter Kruzliak or Peter Urdzik.

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Mytsyk, Y., Borys, Y., Tumanovska, L. et al. MicroRNA-15a tissue expression is a prognostic marker for survival in patients with clear cell renal cell carcinoma. Clin Exp Med 19, 515–524 (2019). https://doi.org/10.1007/s10238-019-00574-7

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