Abstract
Efferocytosis, the process by which phagocytes like macrophages and dendritic cells clear apoptotic cells, is crucial for maintaining tissue homeostasis. However, its function in bladder cancer (BLCA) remains unclear and warrants further exploration. This study seeks to establish a prognostic and treatment response signature based on efferocytosis-related genes (EFRGs) for bladder cancer patients. BLCA-related datasets were sourced from the Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/ ) and the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/ ). A comprehensive analysis was performed on 28 prognostic EFRGs. Clustering analysis was carried out using ConsensusClusterPlus. Prognostic differentially expressed genes (DEGs) were identified based on expression variations across the subtypes. A prognostic model was subsequently developed using least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression. Lastly, a thorough analysis was conducted to explore the relationship between risk scores and the tumor immune microenvironment, somatic mutations, as well as responses to immunotherapy and chemotherapy. Consensus clustering revealed two efferocytosis subtypes, Cluster A and Cluster B, and identified 61 prognostic DEGs between them. A risk scoring model, incorporating four key DEGs-SERPINE2, DPYSL3, CTSE, and KRT16-was constructed and validated. This model successfully stratified patients into high-risk and low-risk groups, with high-risk patients showing worse prognosis, increased immune infiltration, and higher immune checkpoint gene expression. The risk scores also provide insights into patient responsiveness to treatment. In conclusion, we identified four key genes-SERPINE2, DPYSL3, CTSE, and KRT16-that can be used to develop a prognostic model for bladder cancer. These findings may provide valuable molecular targets for the clinical diagnosis and therapeutic strategies of bladder cancer.