Identification of a prognostic molecular signature composed of 3 genes involved in immunity in muscle-invasive bladder cancer.

e16029 Background: Immunotherapy in bladder cancer appears to be promising. The aim of this study was to evaluate the involvement of 33 genes of anti-tumor immunity in a wide range of muscle-invasive bladder cancers (MIBC) and to identify new prognostic markers. Methods: The levels of expression of 33 genes involved in anti-tumor immunity were analyzed by real-time quantitative RT-PCR on a consecutive series of 83 TVIM and 15 normal bladder samples. Tissue samples were taken on a cystectomy patch in patients operated between 2002 and 2006. All patients have signed informed consent. The results of the transcriptomic analysis were confirmed by immunohistochemistry and coupled with survival analysis. Results: Of the 33 genes studied, 24 (72.7%) were significantly overexpressed compared to normal bladder tissue. In univariate analysis, overexpression of OX40L was significantly associated with a pejorative prognosis in terms of recurrence-free survival and overall survival (p = 0.0027 and p = 0.014 respectively) while overexpression of CD8 was associated with a better prognosis (p = 0.024 and p = 0.029 respectively). A clustering analysis allowed us to identify a molecular signature composed of 3 genes ( OX40L, CD8 and TIGIT) allowing to separate the tumors into 3 distinct prognostic subgroups. In a multivariate analysis including all clinico-pathological and molecular factors significant in univariate, molecular signature was an independent prognostic factor in terms of recurrence-free survival and overall survival (p = 0.0007 and p = 0.007 respectively). Conclusions: We identified several genes involved in the immune response during bladder urothelial carcinogenesis, as well as a molecular signature composed of 3 genes ( OX40L, CD8 and TIGIT) associated with MIBC prognosis, suggesting a potential interest in Individual step.