Alteration in expression of pattern-recognition-receptors-signaling- pathways-related genes is associated with immune microenvironment and predicts clinical outcomes in bladder cancer

Background: Although immune checkpoint inhibitors have been utilized to treat advanced bladder cancer, a considerable proportion of patients have resistance to anti-PD1/PD-L1 immunotherapy. Pattern recognition receptors (PRRs) are correlated with host anti-tumor immune response and tumor progression. This study was designed to investigate the impact of PRRs-related genes on tumor immune microenvironment and clinical outcomes of bladder cancer. Methods: We obtained transcriptome data and clinicopathological information of bladder cancer from TCGA database.Pattern-recognition-receptors-signaling-pathwaygene sets were downloaded from the official website of GSEA. Consensus clustering was employed to identify distinct subtypes based on the expression of the PRRs-related genes. CIBERSORT and ssGSEA analyses were employed to evaluate infiltration of various types of immune cellsin the tumor microenvironment. ESTIMATE algorithm was applied to assess intratumoral infiltration of stromal, immune cells and tumor purity. LASSO and stepwise regression analyses were employed to select the prognostic PRRs-related genes, and we constructed a risk model based on these genes via multivariate Cox regression analysis. Results: Two distinct subtypes were identified through consensus clustering. There was significant difference in clinical outcomes, infiltration of immune cells, expression of immune checkpoints and functional pathways between two subtypes. In addition, we identified 9 prognostic genes and constructed a prognostic risk model based on these genes. PRRs-related risk score was confirmed as an independent risk factor for OS of bladder cancer through multivariate Cox analysis. Conclusions: Expression of pattern-recognition-receptors-related genes is closely associated with immune microenvironment and clinical prognosis of bladder cancer.