Myeloid cell differentiation-related gene signature predicts the prognosis and immunotherapy response in bladder cancer

This study aims to identify prognostic and therapy-response biomarkers in bladder cancer (BC) by developing a predictive gene signature based on myeloid cell differentiation-related genes (MCDGs) to enhance patient management. BC patient data from TCGA and GEO were analyzed using non-negative matrix factorization (NMF) to classify subgroups. Survival differences and pathway variations were assessed. A prognostic MCDG model was constructed using univariate Cox regression and LASSO analyses, validated through Kaplan–Meier survival and ROC curves. Clinical relevance, tumor microenvironment (TME), drug response, and immunotherapy potential were evaluated. ACTN1 was verified via qRT-PCR and functional assays, including transwell migration, wound healing, colony formation, and EDU assays. NMF identified two BC subgroups (CA and CB), with CB showing better survival. Six key MCDGs linked to prognosis were identified. High-risk gene profiles correlated with poorer outcomes. Significant differences in immune infiltration, checkpoint expression, TME, and treatment response were observed. Notably, ACTN1 silencing suppressed BC cell proliferation. The MCDG signature predicts BC prognosis and may guide immunotherapy selection. ACTN1 is crucial in BC proliferation, highlighting its potential as a therapeutic target.