title: Using microRNA profiling in urine samples to develop a non-invasive test for bladder cancer.
abstract: Current standard methods used to detect and monitor bladder urothelial cell carcinoma (UCC) are invasive or have low sensitivity. The incorporation into clinical practice of a non-invasive tool for UCC assessment would enormously improve patients' quality of life and outcome. This study aimed to examine the microRNA (miRNA) expression profiles in urines of UCC patients in order to develop a non-invasive accurate and reliable tool to diagnose and provide information on the aggressiveness of the tumor. We performed a global miRNA expression profiling analysis of the urinary cells from 40 UCC patients and controls using TaqMan Human MicroRNA Array followed by validation of 22 selected potentially diagnostic and prognostic miRNAs in a separate cohort of 277 samples using a miRCURY LNA qPCR system. miRNA-based signatures were developed by multivariate logistic regression analysis and internally cross-validated. In the initial cohort of patients, we identified 40 and 30 aberrantly expressed miRNA in UCC compared with control urines and in high compared with low grade tumors, respectively. Quantification of 22 key miRNAs in an independent cohort resulted in the identification of a six miRNA diagnostic signature with a sensitivity of 84.8% and specificity of 86.5% (AUC = 0.92) and a two miRNA prognostic model with a sensitivity of 84.95% and a specificity of 74.14% (AUC = 0.83). Internal cross-validation analysis confirmed the accuracy rates of both models, reinforcing the strength of our findings. Although the data needs to be externally validated, miRNA analysis in urine appears to be a valuable tool for the non-invasive assessment of UCC.
authors.affiliation: Laboratory and Department of Urology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Mengual
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lozano
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ingelmo-Torres
authors.forename: Cristina
authors.initials: C
authors.lastname: Gazquez
authors.forename: María José
authors.initials: MJ
authors.lastname: Ribal
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcaraz
mesh_terms: D014408:Biomarkers, Tumor / Q000652:urine*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000145:classification / Q000652:urine*; D008875:Middle Aged; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000652:urine*; D019459:Urothelium / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: biomarkers; bladder cancer; diagnosis and prognosis; expression signature; microRNA; urine