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Updated: Jan 8, 2026
A Murine Orthotopic Bladder Tumor Model and Tumor Detection System
Published on: January 12, 2017
Targeting PSMB5-induced PANoptosis in bladder cancer: multi-omics insights and TCM candidate discovery
Zhe Chang1,2, Jirong Wang1,2, Jiajia Cao3
1Department of Urology, Second Hospital of Lanzhou University, Lanzhou, China.
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). In vitro research confirmed the biological activities of PSMB5 in BLCA. Molecular docking demonstrated PSMB5's binding affinity with traditional Chinese medicines (TCMs).
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. In vitro findings demonstrated that PSMB5 knockdown inhibited the proliferation and migration of BLCA cells while promoting apoptosis, whereas overexpression has the opposite effect. Molecular docking revealed a robust binding affinity between PSMB5 and five TCMs.
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.
Insights
This study identifies PANoptosis-related genes and PSMB5 as key factors in bladder cancer (BLCA) progression. PSMB5 shows potential as a therapeutic target, with links to traditional Chinese medicines.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Bladder cancer (BLCA) is a prevalent malignancy with high mortality.
- The role of PANoptosis, a programmed cell death pathway, in BLCA is not well understood.
- This research investigates PANoptosis-related genes in BLCA for their molecular mechanisms, prognostic value, and therapeutic potential.
Purpose of the Study:
- To elucidate the role of PANoptosis-related genes in bladder cancer.
- To identify molecular subtypes, prognostic markers, and therapeutic targets within BLCA.
- To explore the association of PSMB5 with BLCA and its potential interaction with traditional Chinese medicines.
Main Methods:
- Differential gene expression analysis of BLCA from TCGA and PANoptosis genes.
- LASSO regression for prognostic model development and machine learning (ML) for gene identification.
- Single-cell sequencing, Mendelian randomization (MR), and in vitro experiments to validate PSMB5 function.
Main Results:
- Identified 98 PANoptosis-associated genes, revealing molecular subgroups A and B in BLCA.
- Developed a prognostic model distinguishing high-risk and low-risk BLCA cohorts with distinct immune profiles.
- PSMB5 identified as a critical risk factor, promoting BLCA cell proliferation and metastasis, with demonstrated binding to five traditional Chinese medicines.
Conclusions:
- A prognostic model using PANoptosis genes aids in BLCA risk stratification and immune microenvironment assessment.
- PSMB5 is a significant therapeutic target for BLCA, with implications for traditional Chinese medicine interventions.
