Three-gene signature predicts disease progression of non-muscle invasive bladder cancer

Abstract

The clinical grades and staging methods currently employed for bladder cancer (BC) are inadequate for assessing treatment outcomes for non-muscle invasive bladder cancer (NMIBC). We have developed a clinically applicable quantitative real-time PCR (qPCR) gene signature to predict the progression of NMIBC. Three genes not previously described for BC were selected from our published progression-related gene classifier data set. Data were drawn from a previous study population and from new cases. Primary NMIBC tissue specimens (n=193) were analyzed by qPCR. Risk scores were then used to rank specimens into high- and low-risk signature groups based on their gene expression. The Kaplan-Meier method and a multivariate Cox regression model were used to identify the prognostic value of the three-gene signature for both recurrence and progression. The Kaplan-Meier estimates revealed significant differences in time-to-recurrence and progression between low- and high-risk signatures (log-rank test, p=0.011 and p<0.001, respectively). The multivariate Cox regression analysis showed that the three-gene risk signature is an independent predictor of bladder tumor progression (hazard ratio, 4.268; 95% CI, 1.542-11.814; p=0.005). In conclusion, our three-gene signature was found to be closely associated with progression among patients with NMIBC.