Using microRNA profiling in urine samples to develop a non-invasive test for bladder cancer

作者:Mengual Lourdes*; Jose Lozano Juan; Ingelmo Torres Mercedes; Gazquez Cristina; Jose Ribal Maria; Alcaraz Antonio
来源:International Journal of Cancer, 2013, 133(11): 2631-2641.
DOI:10.1002/ijc.28274

摘要

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%26apos; 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 (R) 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. %26lt;br%26gt;What%26apos;s new? Accurate urinary tests to detect urothelial cell carcinoma (UCC) would improve patients%26apos; quality of life and outcome. Here, in the first global urine miRNA profiling study of UCC patients, the authors provide a list of dysregulated miRNAs that are candidate clinical biomarkers for the non-invasive assessment of UCC. Furthermore, they describe miRNA panels consisting of a modest number of miRNAs that provide high UCC diagnostic and prognostic accuracy. Although clinical trials are needed to validate the data, the findings open the door to the possibility of implementing an accurate and reliable system for the non-invasive assessment of UCC in clinical routine.

  • 出版日期2013-12-1