Integrated bioinformatic analysis identified a novel prognostic pan-programmed cell death signature for bladder...

Programmed cell death (PCD) refers to a molecularly regulated form of cell death that functions as an essential anticancer defense mechanism and serves as a target of anticancer therapies. Multiple types of PCD comprehensively regulate tumorigenesis and tumor progression and metastasis. However, a systemic exploration of the multiple types of PCD in cancers, especially bladder cancer, is lacking. In this study, we evaluated the expression pattern of genes associated with multiple types of PCD in bladder cancer using the "ssGSEA" method and conceptualized the multiple types of PCD as being collectively involved in "Pan-PCD". Based on the differentially expressed genes related to Pan-PCD, we developed a Pan-PCD-related prognostic signature (PPRPS) to predict patient prognosis via univariate and multivariate Cox regression analysis. The PPRPS is an independent prognostic factor, and the AUC (Area Under Curve) for 3-year overall survival was 0.748. Combined with age and stage, PPRPS displayed excellent predictive ability. Based on the PPRPS, higher levels of immune cell infiltration, tumor microenvironment, and immune checkpoint molecules were observed in the high-PPRPS group. Furthermore, PPRPS enabled accurate risk prediction for metastatic urothelial carcinoma after anti-PD-L1 monoclonal antibody treatment. Patients in the high-PPRPS group had poor prognoses. Docetaxel, staurosporine, and luminespib were identified as potentially effective drugs for high-PPRPS bladder cancer patients. In summary, we developed the Pan-PCD signature to improve the accuracy of bladder cancer prognostic predictions and to provide a novel classification method to guide treatment selection.