Prognosis and immunotherapy significances of a cancer-associated fibroblasts-related gene signature in bladder urothelial carcinoma

Background: The biological significance of cancer-associated fibroblasts (CAFs) in bladder urothelial carcinoma (BUC) warrants further investigation. There is an urgent need to explore the predictive utility of CAF-related genes for prognosis in BUC.

Methods: The transcriptome and clinical data of 407 BUC patients in The Cancer Genome Atlas (TCGA) database were analyzed and a prognostic model was established. A total of 476 BUC cases from the E-MTAB-4321 database were used for validation. A risk model was constructed utilizing CAF-related genes through LASSO Cox regression, investigating its association with prognosis, gene mutations, immune cell infiltration, and drug sensitivity in BUC.

Results: We identified five CAF-related genes (EGFL6, NRSN2, SEMA3D, TM4SF1 and TPST1) in both the TCGA and E-MTAB-4321 datasets, and established a prognostic model using LASSO Cox regression. The high-risk group showed a significant correlation with poor survival. Furthermore, the low-risk group exhibited higher tumor mutational burden and lower levels of immune cell infiltration, and this model holds promise for guiding drug selection in BUC patients.

Conclusions: These findings underscore the pivotal role of CAF-related genes in prognostic prediction for BUC patients. Clinical decision-making and tailored therapeutics stand to benefit from these results, providing a valuable reference for future research endeavors.