Identification of tumor microenvironment-related signature for predicting prognosis and immunotherapy response in patients with bladder cancer

The tumor microenvironment (TME) not only provides fertile soil for tumor growth and development but also widely involves immune evasion as well as the resistance towards therapeutic response. Accumulating interest has been attracted from the biological function of TME to its effects on patient outcomes and treatment efficacy. However, the relationship between the TME-related gene expression profiles and the prognosis of bladder cancer (BLCA) remains unclear. The TME-related genes expression data of BLCA were collected from The Cancer Genome Atlas (TCGA) database. NFM algorithm was used to identify the distinct molecular pattern based on the significantly different TME-related genes. LASSO regression and Cox regression analyses were conducted to identify TME-related gene markers related to the prognosis of BLCA and to establish a prognostic model. The predictive efficacy of the risk model was verified through integrated bioinformatics analyses. Herein, 10 TME-related genes (PFKFB4, P4HB, OR2B6, OCIAD2, OAS1, KCNJ15, AHNAK, RAC3, EMP1, and PRKY) were identified to construct the prognostic model. The established risk scores were able to predict outcomes at 1, 3, and 5 years with greater accuracy than previously known models. Moreover, the risk score was closely associated with immune cell infiltration and the immunoregulatory genes including T cell exhaustion markers. Notably, the predictive power of the model in immunotherapy sensitivity was verified when it was applied to patients with metastatic urothelial carcinoma (mUC) undergoing immunotherapy. In conclusion, TME risk score can function as an independent prognostic biomarker and a predictor for evaluating immunotherapy response in BLCA patients, which provides recommendations for improving patients' response to immunotherapy and promoting personalized tumor immunotherapy in the future.