Because non-muscle-invasive bladder cancer (NMIBC) is clinically heterogeneous, predicting disease progression for patients with bladder cancer still remains a major clinical challenge, despite numerous investigations for NMIBC. In this study we identify a prognostic signature to predict the heterogeneity of NMIBC using an integrative analysis of copy number and gene expression data. We analyzed the copy number and gene expression profile data of bladder cancer obtained from The Cancer Genome Atlas (TCGA) consortium. A prognostic signature based on copy number altered gene was developed and validated in three independent patient cohorts (n = 501). Diverse statistical methods were applied to identify and validate a signature. Of the fourteen significant copy number altered molecules reported previously, ten were significantly correlated between copy number and expression changes in the TCGA dataset. Among them, CCNE1 and its co-expressed genes were significantly associated with disease progression, which was validated in the independent cohorts. The CCNE1 signature was shown to be an independent risk factor by a multivariate analysis (HR 4.99, 95% CI = 1.054 to 23.659, P = 0.043). Lastly, gene network and upstream regulator analyses revealed that NMIBC progression might be mediated by CCND1-CCNE1-SP1 pathways. The prognostic molecular signature defined by copy number and expression changes of CCNE1 suggests a novel diagnostic tool for predicting the likelihood of progression in NMIBC.
Citation Format: In-Sun Chu, Sun-Hee Leem. Bioinformatic identification of prognostic signature defined by copy number alteration and expression of CCNE1 in non-muscle invasive bladder cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-285.