ArticleFrontiers in immunology2025
Targeting PSMB5-induced PANoptosis in bladder cancer: multi-omics insights and TCM candidate discovery.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Bladder cancer (BLCA) is among the most common malignancies worldwide, with significant mortality rates. The function of PANoptosis in BLCA, as a controlled process of programmed cell death, remains largely unelucidated. The study aimed to elucidate the role of PANoptosis-related genes in BLCA and investigate their molecular mechanisms, prognostic significance, and therapeutic potential. Methods: By analyzing differentially expressed genes in BLCA from The Cancer Genome Atlas (TCGA) and PANoptosis-associated genes, we discovered 98 genes associated with PANoptosis. Functional enrichment and consensus clustering identified molecular subtypes linked to these genes. A prognostic model was developed via LASSO regression based on these genes. Subsequent analyses assessed clinical significance, characteristics of the immunological milieu, and treatment responsiveness. Systematic screening with machine learning (ML) identified PSMB5 as a pivotal gene, with its functional importance further clarified using single-cell sequencing and Mendelian randomization analysis (MR). Results: Clustering of 98 PANoptosis-associated genes revealed molecular subgroups A and B. A prognostic approach identified high-risk and low-risk cohorts, revealing considerable disparities in clinical characteristics and immunological landscapes across the groups. ML and MR identified PSMB5 as a risk factor in BLCA. Single-cell sequencing revealed that PSMB5 expression is predominantly associated with three cell lines linked to lymph node metastases. Conclusions: A prognostic model incorporating PANoptosis-related genes was developed for stratifying BLCA risk and assessing the immune microenvironment. PSMB5 has been recognized as a crucial therapeutic target, exhibiting dual importance in the molecular etiology of BLCA and traditional Chinese medicine intervention.
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