Construction and comprehensive analysis of a novel prognostic signature associated with immunogenic cell death molecular subtypes in patients with bladder cancer.

Background: Immunogenic cell death (ICD) triggers adaptive immune responses that aid in anticancer therapy. However, the significance of ICD-associated genes (ICDAGs) in clinical applications and their potential impact on the tumor microenvironment (TME) remains unclear. Methods: The TCGA cohort was divided into different ICD clusters using the method of Consensus clustering. We assessed the clinical results and TME features of various ICD clusters. GSVA quantified the activation of hallmark gene sets. To establish an ICD molecular subtypes-related prognostic model (ICDRPM), we performed LASSO Cox regression analysis on the differentially expressed genes (DEGs) among ICD subtypes. We evaluated the assessment of risk groups by analyzing the proportion of immune cells, the TME, differences in genomic mutation, the efficacy of immunotherapy, and drug sensitivity. To enhance the clinical effectiveness of the ICDRPM, a nomograph was developed. Results: Two distinct molecular subtypes were identified, and changes in ICDRGs were associated with clinical outcomes and TME characteristics of patients. A total of 1162 differentially expressed genes (DEGs) were obtained from two ICD clusters, and an ICDRPS was then developed to predict overall survival (OS). During both internal and external validation, patients classified as high-risk exhibited significantly poorer overall survival compared to those classified as low-risk. Additionally, the ICDRPS (ICD_score) was identified as an independent prognostic indicator for patients with BC, demonstrating excellent predictive performance. Afterward, we constructed a dependable nomogram to improve the practicality of the ICD_score. Furthermore, low-risk individuals showed stronger immunocyte infiltration, higher immune checkpoint expression, and higher IPS-PD-1 combined IPS-CTLA4 scores, indicating a greater response to immune checkpoint inhibitors (ICIs). Moreover, individuals categorized as having low or high risk exhibited contrasting sensitivity to anticancer medications. Conclusions: The model constructed for genes related to ICD provided meaningful clinical implications for immunotherapy, and facilitated individualized treatment for BC patients.