Prognostic Value and Regulatory Mechanism of Immune-Related Genes in Bladder Cancer

Background: Immune-related genes (IRGs) are key contributors to bladder cancer (BLCA) development. Whether IRGs-based prognostic signature can predict the prognosis of BLCA patients deserves to be investigated. Methods: Data were downloaded from the Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) database. The differentially expressed IRGs (DEIRGs) were analyzed through Wilcoxon test. Univariate Cox regression analysis was used to identify the prognostic DEIRGs (PDEIRGs), and multivariate Cox regression analysis was employed to construct a prognostic model. The predictive accuracy and independent forecasting ability were evaluated. Tumor-infiltrating immune cells (TIICs) were obtained through Tumor Immune Estimation Resource (TIMER) website and CIBERSORT method. The correlations between present prognostic signature and clinical variables or TIICs were explored. Furthermore, a transcription factors (TFs)-based regulatory network and enrichment analysis were performed to explore the underlying mechanism. Findings: 3126 DEGs, 261 DEIRGs and 24 PDEIRGs were identified. Ten optimal PDEIRGs were adopted to construct a prognostic model, which can serve as an independent prognostic predictor with excellent predictive accuracy. This model could reflect the clinical variables and TIICs, which further verified its reliability in BLCA prognosis prediction. Besides, several immune-related GO terms and KEGG pathways were significantly enriched, and TFs might involve with PDEIRGs regulating. Interpretation: We find a valuable PDEIRGs-based prognostic signature for BLCA patients and reveal the potential regulatory mechanism. Funding Statement: This study was supported by grants from the National Key Basic Research Development Program (973 Program) (No. 2013CB530500), the National Natural Science Foundation of China (No. 81372225, 81372771, 81772734, 81802935) and the Innovation Capability Support Plan of Shaanxi Province (2020PT-021). Declaration of Interests: The authors declare that they have no competing interests.