The tumor microenvironment and prognostic role of autophagy- and immune-related genes in bladder cancer

Abstract

BACKGROUND: Autophagy-related genes and immune-related genes contribute significantly to the initiation and prognosis of bladder cancer (BLCA). OBJECTIVE: We aimed to explore differentially expressed autophagy-related genes (DEARGs) and immune-related genes (DEIRGs) in BLCA to create a prognostic risk assessment model and gain some insights into BLCA’s molecular underpinnings. METHODS: The prognostic DEARGs and DEIRGs were evaluated for BLCA through The Cancer Genome Atlas (TCGA) database (n= 399) and GSE13507 dataset (n= 165). The BLCA risk model was constructed and verified. The immune score, stromal score, and estimate score in different risk groups were calculated by the ESTIMATE algorithm. Immune infiltration levels were assessed by a single sample gene set enrichment analysis (GSEA) algorithm. RESULTS: In the risk model, AURKA, ACTC1, MYLK, PDGFD, PDGFRA and TNC were significantly associated with the overall survival. The pathways in cancer, T cell receptor signaling pathway and B cell receptor signaling pathway were significantly gathered in the high-risk group. Moreover, the risk score was significantly correlated with infiltrating immune cells, expression of critical immune checkpoints and mismatch repair genes including MSH6, MLH1, and MSH2. CONCLUSIONS: In this study, three DEARGs (AURKA, ACTC1, MYLK) and three DEIRGs (PDGFD, PDGFRA, TNC) were demonstrated to be potential prognostic biomarkers for BLCA patients through bioinformatics methods, which might be novel therapeutic targets and prognostic markers for BLCA, in follow up studies, we will combine experiments to verify this.