Abstract 592: Prognostic index system based on 20 genes for predicting recurrence of non-muscle invasive bladder cancer

Abstract

Abstract Backgrounds There is a crucial need for practical molecular markers of bladder cancer recurrence, despite several molecular signatures for the bladder cancer outcomes have been numerously investigated. Here, we aim to identify a molecular signature consisting of small number of genes to predict disease recurrence in non-muscle invasive bladder cancer (NMIBC) and to assess its usefulness as a practical indicator. Methods Trascriptomic profiling was performed using gene expression data from 103 primary NMIBC specimens (Korean cohort) to identify a signature associated with disease recurrence. The prognostic value of the signature was validated in an independent cohort (European cohort, n = 302). Time-dependent receiver operating characteristic (ROC) curves of recurrence using the nearest neighbour estimation method with a cut-off value of 36 months were used to identify a small number of genes that strongly retain prognostic value. A prognostic index (PI) based on the expression data of 20 genes was developed in the Korean cohort and validated in the European cohort. The association between the 20-gene-based PI method and prognosis of NMIBC patients was assessed using Kaplan-Meier plot, the log-rank test, Cox proportional hazards model, and leave-one-out cross validation methods. Results The determination of gene expression patterns by transcriptome data analysis identified 822 genes associated with disease recurrence. Of the 822 genes, 20 genes which are highly associated with recurrence free survival were detected by time-dependent ROC curves. The PI was developed by using Cox coefficient values of 20 genes in the Korean cohort and its robustness was validated in the European cohort (log-rank test, P < 0.001). The PI was shown to be an independent risk factor by a multivariate analysis and subset stratification according to stage and (hazard ratio = 6.082, 95% confidence interval = 3.280 to 11.279, P < 0.001). The subset analysis also revealed that the PI could identify patients who would benefit from intravesical therapy. Finally, gene network analyses and experimental assays indicated that, among the 20 genes, CA9, ARTS-1 and FGF11 could be important mediators for NMIBC recurrence. Conclusions The PI system based on 20 genes illustrates a novel diagnostic tool to identify NMIBC patients that have a high risk of recurrence. Citation Format: Jong Hwan Kim, Seon-Kyu Kim, Seok-Joong Yun, Wun-Jae Kim, Seon-Young Kim. Prognostic index system based on 20 genes for predicting recurrence of non-muscle invasive bladder cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 592. doi:10.1158/1538-7445.AM2015-592