Immunogenic cell death-related signature predicts prognosis and immunotherapy efficacy in bladder cancer.

Background: Immunogenic cell death (ICD) has been verified as a modality of regulated cell death (RCD). Bladder cancer (BC) is a common malignant tumor and ranks tenth in the incidence of global tumor epidemiology. We conducted this study to understand the relationship between ICD and BC and benefit clinical practice.

Methods: Transcriptome and clinical profiling, mutational data of patients were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. BC patients were divided into ICD-high and -low risk subgroups via consensus clusters. Functional enrichment, somatic mutation analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore the potential mechanism. An ICD-related risk signature was constructed via least absolute shrinkage and selection operator (LASSO) regression analysis. Immune infiltration was investigated and multiplexed immunofluorescence staining was used to validate the BC microenvironment. Immune landscape was summarized to show the potential of immunotherapy.

Results: A total of 18 differentially expressed ICD-related genes in BC were distinguished from normal tissue. We identified two clusters and BC patients were divided into ICD-high and -low subgroups in the TCGA BC cohort. The ICD-high subgroup exhibited worse clinical outcomes, different mutation profiles, different functional enrichment, higher immune infiltration, and better immunotherapy response. An ICD-related risk signature made of seven ICD-related genes was established and shown to have outstanding predictive power of prognosis via LASSO Cox regression.

Conclusions: An ICD-related risk signature was established that provides a promising classification system to predict the prognosis in BC patients accurately. The signature provides a novel strategy for immunotherapy of BC.