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Background   S100 calcium binding protein A8  ( S100A8 ) has been implicated as a prognostic indicator in several types of cancer. However, previous studies are limited in their ability to predict the clinical behavior of the cancer. Here, we sought to identify a molecular signature based on  S100A8  expression and to assess its usefulness as a prognostic indicator of disease progression in non-muscle invasive bladder cancer (NMIBC).    Methods  We used 103 primary NMIBC specimens for microarray gene expression profiling. The median follow-up period for all patients was 57.6 months (range: 3.2 to 137.0 months). Various statistical methods, including the leave-one-out cross validation method, were applied to identify a gene expression signature able to predict the likelihood of progression. The prognostic value of the gene expression signature was validated in an independent cohort (n = 302).    Results  Kaplan-Meier estimates revealed significant differences in disease progression associated with the expression signature of  S100A8 -correlated genes (log-rank test,  P  < 0.001). Multivariate Cox regression analysis revealed that the expression signature of  S100A8 -correlated genes was a strong predictor of disease progression (hazard ratio = 15.225, 95% confidence interval = 1.746 to 133.52,  P  = 0.014). We validated our results in an independent cohort and confirmed that this signature produced consistent prediction patterns. Finally, gene network analyses of the signature revealed that  S100A8 ,  IL1B , and  S100A9  could be important mediators of the progression of NMIBC.    Conclusions  The prognostic molecular signature defined by  S100A8 -correlated genes represents a promising diagnostic tool for the identification of NMIBC patients that have a high risk of progression to muscle invasive bladder cancer.

Identification of S100A8-correlated genes for prediction of disease progression in non-muscle invasive bladder cancer