The interplay between angiogenesis-associated genes and molecular, clinical, and immune features in bladder cancer.

Abstract

Background: Immunotherapy plays an important role in the treatment of bladder cancer (BLCA), with outcomes influenced by the tumor microenvironment (TME). Angiogenesis, a hallmark of cancer progression, shapes the TME and impacts immunotherapy efficacy. However, its specific role in BLCA remains underexplored.

Methods: We analyzed 268 angiogenesis-related genes (ARGs) across ten gene sets using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Through unsupervised clustering, we identified ARG-based subtypes and developed an ARG scoring system to quantify angiogenesis activity. The ARG score was correlated with clinical outcomes, immune cell infiltration, and immunotherapy response. Functional validation was performed using in vitro assays.

Results: Two distinct ARG clusters exhibited significant differences in immune profiles, clinical outcomes, and functional characteristics. Patients in the high ARG cluster had poorer survival but showed enhanced responsiveness to immune checkpoint inhibitors (ICIs). The novel ARG score demonstrated strong predictive power for immunotherapy efficacy and survival outcomes.

Conclusion: ARG expression patterns profoundly impact the TME, clinical outcomes, and immunotherapy response in BLCA. The ARG score is a novel biomarker for stratifying patients and optimizing treatment strategies. These findings may contribute to clarifying the characteristics of TME and enable the exploration of more potent immunotherapy strategies.