INTRODUCTION: Urinary microRNAs (miRNAs) are emerging as a clinically useful tool for early and non-invasive detection of various types of cancer. The aim of this study was to evaluate whether let-7 family miRNAs differ in their urinary concentrations between renal cell carcinoma (RCC) cases and healthy controls. MATERIALS AND METHODS: In the case-control study, 69 non-metastatic clear-cell RCC patients and 36 gender/age-matched healthy controls were prospectively enrolled. Total RNA was purified from cell-free supernatant of the 105 first morning urine specimens. Let-7 family miRNAs were determined in cell-free supernatant using quantitative miRNA real-time reverse-transcription PCR and absolute quantification approach. RESULTS: Concentrations of all let-7 miRNAs (let-7a, let-7b, let-7c, let-7d, let-7e and let-7g) were significantly higher in urine samples obtained from RCC patients compared to healthy controls (P < 0.001; P < 0.001; P = 0.005; P = 0.006; P = 0.015 and P = 0.002, respectively). Subsequent ROC analysis has shown that let-7a concentration possesses good ability to differentiate between cases and controls with area under curve being 0.8307 (sensitivity 71%, specificity 81%). CONCLUSIONS: We have shown that let-7 miRNAs are abundant in the urine samples of patients with clear-cell RCC, and out of six let-7 family members, let-7a outperforms the others and presents promising non-invasive biomarker for the detection of RCC.

Department of Oncology Thomayer Hospital and Charles University 1st Faculty of Medicine Prague Czech Republic

Department of Urology University Hospital Brno and Masaryk University Brno Brno Czech Republic

Masaryk Memorial Cancer Institute Department of Comprehensive Cancer Care Brno Czech Republic

Masaryk Memorial Cancer Institute Department of Urologic Oncology Brno Czech Republic

Masaryk University Central European Institute of Technology Brno Czech Republic

Masaryk University Central European Institute of Technology Brno Czech Republic Masaryk Memorial Cancer Institute Department of Comprehensive Cancer Care Brno Czech Republic

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$a Fedorko, Michal $u Department of Urology, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic.

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$a Detection of let-7 miRNAs in urine supernatant as potential diagnostic approach in non-metastatic clear-cell renal cell carcinoma / $c M. Fedorko, J. Juracek, M. Stanik, M. Svoboda, A. Poprach, T. Buchler, D. Pacik, J. Dolezel, O. Slaby,

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$a INTRODUCTION: Urinary microRNAs (miRNAs) are emerging as a clinically useful tool for early and non-invasive detection of various types of cancer. The aim of this study was to evaluate whether let-7 family miRNAs differ in their urinary concentrations between renal cell carcinoma (RCC) cases and healthy controls. MATERIALS AND METHODS: In the case-control study, 69 non-metastatic clear-cell RCC patients and 36 gender/age-matched healthy controls were prospectively enrolled. Total RNA was purified from cell-free supernatant of the 105 first morning urine specimens. Let-7 family miRNAs were determined in cell-free supernatant using quantitative miRNA real-time reverse-transcription PCR and absolute quantification approach. RESULTS: Concentrations of all let-7 miRNAs (let-7a, let-7b, let-7c, let-7d, let-7e and let-7g) were significantly higher in urine samples obtained from RCC patients compared to healthy controls (P < 0.001; P < 0.001; P = 0.005; P = 0.006; P = 0.015 and P = 0.002, respectively). Subsequent ROC analysis has shown that let-7a concentration possesses good ability to differentiate between cases and controls with area under curve being 0.8307 (sensitivity 71%, specificity 81%). CONCLUSIONS: We have shown that let-7 miRNAs are abundant in the urine samples of patients with clear-cell RCC, and out of six let-7 family members, let-7a outperforms the others and presents promising non-invasive biomarker for the detection of RCC.

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$a Juracek, Jaroslav $u Masaryk University, Central European Institute of Technology, Brno, Czech Republic.

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$a Stanik, Michal $u Masaryk Memorial Cancer Institute, Department of Urologic Oncology, Brno, Czech Republic.

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$a Svoboda, Marek $u Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno, Czech Republic.

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$a Poprach, Alexandr $u Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno, Czech Republic.

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$a Buchler, Tomas $u Department of Oncology, Thomayer Hospital and Charles University First Faculty of Medicine, Prague, Czech Republic.

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$a Pacik, Dalibor $u Department of Urology, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic.

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$a Dolezel, Jan $u Masaryk Memorial Cancer Institute, Department of Urologic Oncology, Brno, Czech Republic.

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$a Slaby, Ondrej $u Masaryk University, Central European Institute of Technology, Brno, Czech Republic. Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno, Czech Republic.

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