title: microRNA expression profile in a large series of bladder tumors: identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer.
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.
authors.affiliation: Department of Urology, Hôpital Cochin, AP-HP, Paris F-75014, France. gg_pignot@yahoo.fr
authors.forename: Géraldine
authors.initials: G
authors.lastname: Pignot
authors.forename: Geraldine
authors.initials: G
authors.lastname: Cizeron-Clairac
authors.forename: Sophie
authors.initials: S
authors.lastname: Vacher
authors.forename: Aurelie
authors.initials: A
authors.lastname: Susini
authors.forename: Sengül
authors.initials: S
authors.lastname: Tozlu
authors.forename: Annick
authors.initials: A
authors.lastname: Vieillefond
authors.forename: Marc
authors.initials: M
authors.lastname: Zerbib
authors.forename: Rosette
authors.initials: R
authors.lastname: Lidereau
authors.forename: Bernard
authors.initials: B
authors.lastname: Debre
authors.forename: Delphine
authors.initials: D
authors.lastname: Amsellem-Ouazana
authors.forename: Ivan
authors.initials: I
authors.lastname: Bieche
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D019042:Muscle Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C533896:MIRN200 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; D012333:RNA, Messenger