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.

2nd Department of Surgery Faculty of Medicine Masaryk University and St Anne's University Hospital Brno Czech Republic

Department of General Medicine Faculty of Medicine Slovak Medical University Bratislava Slovakia

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

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

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

Department of Radiology Danylo Halytsky Lviv National Medical University Lviv Ukraine

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

Faculty of Medicine University of Oviedo and Central University Hospital of Asturias Oviedo Spain

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

Zobrazit více v PubMed

J Cancer Res Clin Oncol. 2018 Dec;144(12):2313-2318 PubMed

Eur Urol. 2010 Jan;57(1):102-9 PubMed

Chem Biol Drug Des. 2016 Mar;87(3):321-34 PubMed

Int J Mol Sci. 2018 Apr 01;19(4):null PubMed

Semin Cancer Biol. 2019 Oct;58:47-55 PubMed

Cancer Biomark. 2017;18(1):11-17 PubMed

Cent European J Urol. 2018;71(3):295-303 PubMed

Clin Exp Med. 2018 May;18(2):165-175 PubMed

Cancer Manag Res. 2017 Nov 21;9:679-689 PubMed

Biochemistry (Mosc). 2015 Mar;80(3):276-83 PubMed

Int J Mol Sci. 2017 Oct 02;18(10):null PubMed

Semin Cancer Biol. 2019 Oct;58:56-64 PubMed

J Mol Cell Biol. 2011 Jun;3(3):159-66 PubMed

Oncol Rep. 2017 Oct;38(4):1995-2002 PubMed

Front Oncol. 2018 Jun 11;8:224 PubMed

J Clin Oncol. 2004 Aug 15;22(16):3316-22 PubMed

Tumour Biol. 2017 May;39(5):1010428317695525 PubMed

Biochim Biophys Acta. 2011 Oct;1813(10):1793-802 PubMed

J Cell Biochem. 2018 Nov;119(11):8737-8742 PubMed

Clin Exp Med. 2018 May;18(2):177-190 PubMed

Am J Pathol. 2012 May;180(5):1787-97 PubMed

Gene. 2018 Dec 30;679:241-252 PubMed

Ann Oncol. 2016 Sep;27(suppl 5):v58-v68 PubMed

Cell Death Differ. 2010 Feb;17(2):215-20 PubMed

PLoS One. 2014 Nov 26;9(11):e114096 PubMed

Lancet Oncol. 2015 Mar;16(3):293-300 PubMed

Eur J Cancer. 2013 Apr;49(6):1374-403 PubMed

Lancet Oncol. 2013 Feb;14(2):141-8 PubMed

Tumour Biol. 2016 Oct;37(10):13941-13950 PubMed

Anticancer Res. 2015 Jan;35(1):123-7 PubMed

Clin Transl Oncol. 2015 Jul;17(7):504-10 PubMed

J Cell Biochem. 2019 Mar;120(3):3415-3422 PubMed

PLoS One. 2017 Jul 3;12(7):e0179437 PubMed

Int J Mol Sci. 2018 Feb 26;19(3):null PubMed

Pathophysiology. 2018 Dec;25(4):335-345 PubMed

Int Urol Nephrol. 2018 May;50(5):851-859 PubMed

Oncol Res. 2016;24(3):145-51 PubMed

Cancer. 2005 Feb 1;103(3):625-9 PubMed

J Urol. 2012 Aug;188(2):391-7 PubMed

Cancer. 2017 Jul 1;123(13):2524-2534 PubMed

Systemic treatment of the metastatic renal cell carcinoma: usefulness of the apparent diffusion coefficient of diffusion-weighted MRI in prediction of early therapeutic response