MicroRNAs in renal cell carcinoma

HÉŽOVÁ, Renata, Martina RÉDOVÁ, Robert ILIEV, Alexandr POPRACH, Jana NEKVINDOVÁ, Radek LAKOMÝ, Marek SVOBODA, Rostislav VYZULA and Ondřej SLABÝ. MicroRNAs in renal cell carcinoma. In 3rd ICCTI Workshop - MicroRNAs in Oncology. 2012.

Basic information

• Original name: MicroRNAs in renal cell carcinoma
• Authors: HÉŽOVÁ, Renata, Martina RÉDOVÁ, Robert ILIEV, Alexandr POPRACH, Jana NEKVINDOVÁ, Radek LAKOMÝ, Marek SVOBODA, Rostislav VYZULA and Ondřej SLABÝ.
• Edition: 3rd ICCTI Workshop - MicroRNAs in Oncology, 2012.

Other information

• Original language: English
• Type of outcome: Conference abstract
• Field of Study: 30200 3.2 Clinical medicine
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• Organization unit: Central European Institute of Technology
• Keywords in English: microRNAs; oncology; renal cell carcinoma

Abstract

Renal cell carcinoma (RCC) is the most common neoplasm of adult kidney and having the highest mortality rate at over 40%. Renal tumors are commonly asymptomatic in early stages and although surgical resection remains the best therapy for RCC, after the curative nephrectomy, 20-40% patients will develop recurrence. Our aim was to identify standard serum biomarkers used for diagnosis or early detection of recurrence of RCC patients. Second aim was to identify prognostic tissue miRNAs, which could distinguish patients with high risk of relapse after nephrectomy to individualize therapy for these patients. We performed TaqMan Low Density arrays in tumors of different prognostic groups of 77 RCC patients and in blood serum of 15 RCC patients and 12 matched healthy controls. We identified tumor relapse signature based on the expression of 64 miRNAs differentially expressed between relapse-free RCC patients and RCC patients who developed relapse. In validation study, we successfully confirmed that expression level of 6 miRNAs were lower in the tumors of patients who developed relapse, moreover, the lowest levels of these miRNAs were observed in primary metastatic tumors. By using Kaplan-Meier analysis we identified that miR-127-3p, miR-145 and miR-126 significantly corelate with relapse-free survival of non-metastatic RCC patients. In serum, we identified 30 miRNAs differentially expressed between RCC patients and healthy controls. In independent validation group we successfully validated 2 of them: levels of miR-378 were increased (p = 0,0003, AUC = 0,71), miR-451 levels were decreased (p<0,0001) in serum of RCC patients. Combination of circulating miR-378 and miR-451 enables identification of RCC patients with the sensitivity of 81%, specificity 83% and AUC 0,86. Identified tissue miRNAs might be used for identification of RCC patients at high risk of early relapse after nephrectomy in clinical practice. Circulating miRNAs in serum are promising biomarkers in RCC diagnostics.