MicroRNA expression profile in a large series of bladder tumors: Identification of a 3‐miRNA signature associated with aggressiveness of muscle‐invasive bladder cancer1. Issue 11 (25th February 2013)

• Record Type: Journal Article
• Authors: Pignot, Géraldine; Cizeron‐Clairac, Geraldine; Vacher, Sophie; Susini, Aurelie; Tozlu, Sengül; Vieillefond, Annick; Zerbib, Marc; Lidereau, Rosette; Debre, Bernard; Amsellem‐Ouazana, Delphine; Bieche, Ivan
• Is Part Of: International journal of cancer. Volume 132:Issue 11(2013:Jun. 01)
• Page Start: 2479
• Page End: 2491
• Publication Date: 2013-02-25
• Subjects: bladder cancer -- microRNA -- molecular marker -- prognostic factor -- RT‐PCR; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.27949
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: The aim of this study was to evaluate the expression levels of microRNAs (miRNAs) in bladder tumors in order to identify miRNAs involved in bladder carcinogenesis with potential prognostic implications. Expression levels of miRNAs were assessed by quantitative real‐time RT‐PCR in 11 human normal bladder and 166 bladder tumor samples (86 non‐muscle‐invasive bladder cancer (NMIBC) and 80 muscle‐invasive bladder cancer (MIBC)). The expression level of 804 miRNAs was initially measured in a well‐defined series of seven NMIBC, MIBC and normal bladder samples (screening set). The most strongly deregulated miRNAs in tumor samples compared to normal bladder tissue were then selected for RT‐PCR validation in a well‐characterized independent series of 152 bladder tumors (validation set), and in six bladder cancer cell lines. Expression levels of these miRNAs were tested for their association with clinical outcome. A robust group of 15 miRNAs was found to be significantly deregulated in bladder cancer. Except for two miRNAs, miR‐146b and miR‐9, which were specifically upregulated in MIBC, the majority of miRNAs ( n = 13) were deregulated in the same way in the two types of bladder tumors, irrespective of pathological stage : three miRNAs were upregulated ( miR‐200b, miR‐182 and miR‐138 ) and the other 10 miRNAs were downregulated ( miR‐1, miR‐133a, miR‐133b, miR‐145, miR‐143, miR‐204, miR‐921, miR‐1281, miR‐199a and miR‐199b ). A 3‐miRNA signature ( miR‐9, miR‐182 and miR‐200b ) was found to be related to MIBC tumor aggressiveness and was associated with both recurrence‐free and overall survival in univariate analysis with a trend to significance in the multivariate analysis ( p = 0.05). Our results suggested a promising individual prognostic value of these new markers. Abstract : What's new? MicroRNAs (miRNAs) are potential markers of disease prognosis for certain types of cancer, and thus their identification and characterization could benefit patients, as well as lead to the development of novel therapies. These implications are highlighted in this large‐scale RT‐PCR study, which involved the analysis of 804 miRNAs and 166 human bladder tumors. Three miRNAs, miR‐9, miR‐182, and miR‐200b, were found to be associated specifically with tumor aggressiveness and prognosis in muscle‐invasive bladder cancer. The findings warrant further investigation of miRNAs as prognostic markers of bladder cancer, which is the fifth most common malignancy in economically advanced countries.