Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma

Martina Redova,Robert Iliev,Radek Lakomy,Alexandr Poprach,Lenka Radova,Ondrej Slaby,Rostislav Vyzula,Jana Nekvindova,Marek Svoboda

doi:10.1186/1479-5876-10-55

Abstract

BackgroundThere is no standard serum biomarker used for diagnosis or early detection of recurrence for renal cell carcinoma (RCC) patients. MicroRNAs (miRNAs) are abundant and highly stable in blood serum, and have been recently described as powerful circulating biomarkers in a wide range of solid cancers. Our aim was to identify miRNA signature that can distinguish the blood serum of RCC patients and matched healthy controls and validate identified miRNAs as potential biomarkers for RCC.MethodsIn the screening phase of the study, blood serum of 15 RCC patients and 12 matched healthy controls were analyzed by use of the TaqMan Low-Density Arrays enabling parallel identification of expression levels of 667 miRNAs through qRT-PCR-based approach. In the validation phase, identified miRNAs were further evaluated on the independent group of 90 RCC patients and 35 matched healthy controls by use of individual qRT-PCR assays and statistically evaluated.ResultsWe identified 30 miRNAs differentially expressed between serum of RCC patients and healthy controls: 19 miRNAs were up-regulated and 11 miRNAs were down-regulated in RCC patients. MiR-378, miR-451 and miR-150 were further evaluated in the independent group of patients, and two of them were successfully validated: levels of miR-378 were increased (p = 0.0003, AUC = 0.71), miR-451 levels were decreased (p < 0.0001, AUC = 0.77) in serum of RCC patients. Combination of miR-378 and miR-451 enable identification of RCC serum with the sensitivity of 81%, specificity 83% and AUC = 0.86.ConclusionsCirculating miRNAs in serum are promising biomarkers in RCC.

Highlights

We determined the miRNA expression profile of 667 miRNAs in serum from ccRCC patients (n = 15) using TaqMan Low Density Arrays technology, and compared to the expression profile of healthy individuals (n = 12); the miRNA expression levels were normalized to miR-16, the mean expression levels were calculated and data analyzed by use of the microarray biostatistical approaches
We observed 30 miRNAs differentially expressed between serum of ccRCC patients and healthy controls: 19 miRNAs were up-regulated in ccRCC patients and 11 miRNAs were down-regulated (Figure 1, Table 2)
Multivariate logistic regression analysis showed that both miR-378 and miR-451 could serve as potential biomarkers for distinguishing between renal cell carcinoma (RCC) and healthy controls, and even that their combination could improve the stratification power characterized with area under curve (AUC) of 0.86 and the sensitivity of 81% and specificity 83% (Figure 3)

Summary

Introduction

There is no standard serum biomarker used for diagnosis or early detection of recurrence for renal cell carcinoma (RCC) patients. MicroRNAs (miRNAs) are abundant and highly stable in blood serum, and have been recently described as powerful circulating biomarkers in a wide range of solid cancers. There is no standard serum biomarker used for diagnosis or early detection of recurrence for RCC patients. MiRNA signatures in blood are similar in men and women, as well as individuals of different age [7]. These circulating miRNAs had shown great potential to serve as a novel biomarker for non-invasive diagnosis and prognosis of plenty kinds of diseases, such as cancer, and even physiological conditions such as prenatal screening. Following the release from cells, circulating miRNAs originate from (i) microvesicles (released by exocytosis), (ii) exosomes (formed via invagination of the early endosome and released upon fusion of late endosome with plasma membrane), and (iii) apoptotic vesicles and/or senescent bodies [7,8,9]

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