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

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.

MicroRNA-15a expression measured in urine samples as a potential biomarker of renal cell carcinoma.

INTRODUCTION: Currently, there is no accurate diagnostic molecular biomarker for renal cell carcinoma (RCC). The aim of this study was to assess the expression of microRNA-15a (miR-15a) in urine of patients with RCC and to evaluate its potential as a diagnostic molecular biomarker. MATERIALS AND METHODS: In total, 67 patients with solid renal tumors were enrolled: clear-cell RCC (ccRCC, n = 22), papillary RCC (pRCC, n = 16), chromophobe RCC (chRCC, n = 14), oncocytoma (n = 8), papillary adenoma (n = 2) and angiomyolipoma (n = 5). MiRNA-15a expression levels measurement in urine were performed using qPCR. Urine of 15 healthy volunteers without kidney pathology was used as control. RESULTS: We observed a difference in mean miR-15a expression values in groups of pre-operative patients with RCC, benign renal tumors and healthy persons (2.50E-01 ± 2.72E-01 vs 1.32E-03 ± 3.90E-03 vs 3.36E-07 ± 1.04E-07 RFU, respectively, p < 0.01). There was no difference in miR-15a expression between ccRCC, pRCC and chRCC (p > 0.05). Direct association between RCC size and miR-15a expression values was obtained (Pearson correlation coefficient-0.873). On the 8th day after nephrectomy, mean expression value in patients with RCC decreased by 99.53% (p < 0.01). MiR-15a expression differentiated RCC from benign renal tumors with 98.1% specificity, 100% sensitivity at a cut-off value of 5.00E-06 RFU, with AUC-0.955. CONCLUSIONS: MiR-15a expression measured in urine may be used as diagnostic molecular biomarker for RCC.

Potential clinical applications of microRNAs as biomarkers for renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) accounts for 3% of adult malignancies and more than 90% of kidney neoplasms. High rates of undiagnostic percutaneous kidney biopsies and difficulties in reliable pre-operative differentiation between malignant and benign renal tumors using contemporary imaging techniques result in large numbers of redundant surgeries. Absence of specific biomarkers for early detection and monitoring complicates on-time diagnosis of the disease and relapse. For the patients followed up after having a nephrectomy, a noninvasive and sensitive biomarker enabling early detection of disease relapse would be extremely useful. MATERIAL AND METHODS: The study is a review of recent knowledge regarding potential clinical applications of microRNAs (miRNAs) as biomarkers of RCC. RESULTS: MicroRNAs are essential regulators of various processes such as cell proliferation, differentiation, development and death; they have been implicated in diverse biological and pathological processes in RCC. There is a class of miRNAs that promote RCC development (oncomirs) and a class of miRNAs that negatively regulate oncogenes, suppress tumor growth and invasion, and thus could be considered treatment agents (anti-oncomirs). Separate miRNAs and specific miRNAs expression profiles have been identified, enabling early detection of the disease, prediction of response to systemic therapy, or prognostication of biological behavior of the disease. CONCLUSIONS: The miRNA network analysis and gene profiling may help to identify the most sensible molecular signatures of RCC that can be used for diagnostic purposes, as well as poor prognosis signatures and poor therapeutic response signatures in patients who undergo systemic therapy.