Abstract 4343: Molecular identification of bladder cancer gene expression subtypes

Abstract

Abstract Bladder urothelial carcinoma (BLCA) comprises two main types: non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). To discovery the subtype of BLCA, we used gene expression data from 165 patient cohort (102 NMIBC, 63 MIBC). Three other gene expression data sets including the Sweden 1 cohort (97 NMIBC, 45 MIBC), the Sweden 2 cohort (213 NMIBC, 93 MIBC), and 408 MIBC sample from The Cancer Genome Atlas (TCGA) and 476 sample (460 NMIBC, 16 MIBC, the multicenter European UROMOL consortium). For selection of subtype-specific gene set, we used significance analysis of microarrays (SAM). Then, subtype-specific genes were trained by prediction analysis for microarrays (PAM) to build a classifier. Clustering analyses were applied to gene expression data of training set identified four molecular subtypes with different clinical outcomes. The majority of patients with class 1 were the low-grade NMIBC and associated with the prognosis of NMIBC, for cancer-specific survival (P =0.003, log-rank test). Class 2 patients, characterized by FGFR3 overexpression and downregulated immune pathways, showed the intermediate prognosis. Class 3 tumors showed high expression of cell-cycle genes and downregulated notch signaling pathway. Furthermore, high-grade NMIBC were predominantly found in class 3, indicating that NMIBC patients classified as class 3 would be more likely to progress to MIBC. Class 4 tumors, mainly composed of MIBC, were characterized by high expression of immune-related genes which is positively associated with potential response to immunotherapy. We further validated the BLCA subtypes in four independent data sets (n = 1,471), including the RNA-seq data set, by applying the 786-gene classifier onto the data sets. As expected, the progression rate of NMIBC patients classified as class 3 was significantly increased compared with other three classes in the RNA-seq data set (P < 0.001, log-rank test). Citation Format: In-Sun Chu, Bic-Na Song, Sun-Hee Leem. Molecular identification of bladder cancer gene expression subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4343.