Identification and validation of an immune-related gene-based prognostic index for bladder cancer

Bladder cancer (BLCA) is a common malignancy arising from the urinary bladder and therapeutic options are limited. However, the mechanisms underlying BLCA development are poorly understood. In this study, robust rank aggregation was used to integrate five GEO BLCA microarray datasets for identifying differentially expressed genes (DEGs) between non-muscular invasive BLCA and muscular invasive BLCA. One-hundred fifty-four DEGs related to the degree of BLCA infiltration, including 24 immune-related genes (IRGs), were identified. Missense mutations were the most common type in IRGs. Ten hub IRGs were identified by protein-protein interaction network analysis. Gene set enrichment analysis and gene set variation analysis of two novel BLCA-related genes (TYROBP and FCER1G) revealed that they were related to immunity. Nine survival-related IRGs were identified, and their potential regulation by transcription factors was analyzed. An immune-related gene-based prognostic index (IRGPI) comprising CTSE, CXCL10, FAM3B, MMP9, OLR1, and S100P was constructed using multivariate analysis. The reliability of the IRGPI was evaluated using independent datasets, and correlations between the IRGPI and clinicopathological characteristics, as well as the immune microenvironment, were evaluated. Finally, a nomogram was established to evaluate the prognosis of patients with BLCA. Our data provide new insights into the pathogenesis of BLCA and target genes for immunotherapy. The application of molecular markers for hierarchical prediction paves the way for precision medicine.