Association of Angiogenesis-Related Gene Mutations with Tumor Microenvironment and their Clinical Significance in Bladder Cancer

Abstract Background: Immunotherapy has emerged as a crucial treatment option for various types of cancer, including bladder cancer (BC). The effectiveness of immunotherapy depends on the intricate interplay between the tumor microenvironment (TME) and cancer cells. Angiogenesis, a key feature of cancer progression, has not been fully understood in relation to clinical outcomes, immune cell infiltration, and the impact on immunotherapy in BC. Methods: We systematically evaluated the expression patterns of genes in 10 predefined angiogenesis-related gene (ARG) sets using data from TCGA and GEO cohorts, and subsequently investigated the association between angiogenesis and transcriptional profiles, as well as their impact on prognosis and immune cell infiltration. An ARG_Score was developed to quantify the angiogenesis subtypes of individual patients, and its potential for predicting prognosis and therapeutic response in BC was assessed. Results: ARG mutations were identified to be associated with the clinicopathological characteristics, prognosis, and infiltrating TME of patients. The established ARG_Score was significantly associated with the tumor microenvironment and clinical outcomes. A lower ARG_Score was characterized by elevated immune activation and better overall survival (OS). Moreover, the ARG_Score was markedly correlated with drug susceptibility. A nomogram based on the ARG_Score was shown to have high reliability in predicting the OS of BC. Conclusion: ARG mutations affect the TME, clinicopathological features and prognosis of BC. Utilizing ARG_Score enables the prediction of patients' response to immunotherapy or chemotherapy and improves the accuracy of prognosis prediction.