Identification of a risk model for prognostic and therapeutic prediction in bladder urothelial carcinoma based on infiltrating CD8+ T cells

Background

With increasing evidence indicating that immune cells significantly contribute to tumor progression, elucidating their role in tumor prognosis and therapy has become imperative. This study aims to thoroughly characterize tumor-infiltrating immune cells in bladder cancer (BLCA) and identify key immune cells and gene models associated with prognosis and therapeutic outcomes in BLCA.

Methods

Initially, we assessed the relationship between the abundance of infiltrating immune cells and prognosis, CD8⁺T cell was selected to establish the risk model, which was constructed based on five key genes. Then ROC curve was drawn to demonstrate the risk model had high prognosis predictive value in BLCA.

Results

Our correlation analysis revealed that riskscore was negatively associated with several steps of the tumor immune cycle. Additionally, the risk score exhibited a negative correlation with the expression levels of CD8,CD274,IFNG, Merck18, and several common immune checkpoints. Furthermore, the tumor exclusion score and Tumor Immune Dysfunction and Exclusion (TIDE) score were significantly higher in the high-score group compared to the low-score group. Notably, the risk score demonstrated a negative correlation with the enrichment score of immunotherapy-related pathways, indicating that the therapeutic benefit was greater in the low-score group than in the high-score group. Then, a total of 171 chemotherapy and targeted drugs were identified. Subsequently, immunohistochemistry, EDU and Western blot were used to verify our result.

Conclusions

Our results confirmed that the tumor infiltration CD8⁺ T cells in tumors plays a critical role in the prognosis and treatment of bladder cancer (BLCA). This insight may offer new directions and inspiration for prognostic prediction and therapeutic strategies for bladder cancer in the future.