Identification and Validation of an Immune-Related Gene-Based Prognostic Index for Bladder Cancer

Abstract

Background: Bladder cancer (BLCA) is a common malignant tumour of the urinary system. Knowledge of the mechanism of and treatment methods for BLCA remain limited. Methods: Robust rank aggregation was used to integrate five GEO bladder cancer microarray datasets for identifying differentially expressed genes (DEGs) between NMIBC and MIBC. An immune-related gene (IRG)-based prognostic index (IRGPI) 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 patient prognosis with BLCA. Findings: We identified 154 DEGs related to the degree of BLCA infiltration, including 24 IRGs. Missense mutation was the most common mutation type in IRGs. Ten hub IRGs were identified by protein-protein interaction network analysis. GSEA and GSVA 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 analysed. An independent IRGPI (CTSE, CXCL10, FAM3B, MMP9, OLR1, and S100P) was established, and was confirmed to be related to tumour stage, tumour grade, T stage, and N stage. The nomogram could effectively predict the prognosis of BLCA patients. Importantly, the IRGPI reflected infiltration by several types of immune cells. Interpretation: Our data provide new insights in the pathogenesis of BLCA and target genes for immunotherapy. The application of molecular markers for hierarchical prediction paves the way to precision medicine. Funding: This study was financially supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (grant number: 2018-I2M-1-002) and the Beijing Hospital Clinical Research 121 Project (BJ-2018-090). Declaration of Interest: The authors have declared no competing interests.