Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer

Abstract

Bladder cancer is one of the most common malignant tumors of the urinary system that seriously threatens the health of a population. In recent years, the application of immunotherapy has significantly changed the treatment of bladder cancer, but only some patients can benefit from the treatment with immune-checkpoint inhibitors. Many problems are unsolved in the field of bladder cancer immunotherapy, especially in the search for genes that are critical to the level of immune cell infiltration and new effective therapeutic targets. We attempted to use bioinformatics analysis to identify immune gene markers related to the prognosis of bladder cancer and to establish a prognostic signature for bladder cancer patients based on their immune gene expression profiles. We used univariate Cox proportional hazards regression analysis, the least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox proportional hazards regression analysis from The Cancer Genome Atlas bladder cancer cohort (TCGA-BLCA). Fifteen genes related to prognosis were screened using the survival analysis, correlation analysis, cancer and adjacent cancer differential expression analysis, and mutation analysis. The potential biological role of these genes was determined using survival analysis and principal component analysis (PCA). The receiver operating characteristic (ROC) curve assesses the prognostic value of the predictive signature. The gene ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG), Gene set enrichment analysis (GSEA), and other methods were used to reveal the differential gene enrichment in the signaling pathways and cellular processes of high- and low-risk groups. The single-sample GSEA (ssGSEA) method was used to quantify the infiltration levels of 24 immune cells in the tumor immune microenvironment and these immune genes were found to be closely related to the tumor immune microenvironment. In summary, we screened 15 immune genes that were closely related to bladder cancer overall survival (OS) and may be potential prognostic indicators of bladder cancer. They may have research and clinical application value in bladder cancer immunotherapy. We used 15 immune genes to construct a new immune-related gene signature that was verified and could be helpful in improving individualized prognosis of patients with bladder cancer.