ORIGINAL RESEARCH article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
This article is part of the Research TopicComparative Genomics and Functional Genomics Analyses in CancerView all 11 articles
Development of a Prognostic Model Related to Mitochondria and programmed cell death related genes in Bladder Cancer
Provisionally accepted
- 1Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China
- 2Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
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Background: Various forms of programmed cell death (PCD) play a crucial role in regulating cancer development and spread, with mitochondria as key organelles executing PCD. In this study, mitochondrial and PCD-related prognostic genes in bladder cancer (BLCA) were explored and prognostic models constructed. Methods: The GSE32894, GSE13507 and The Cancer Genome Atlas (TCGA)-BLCA datasets for BLCA were retrieved from public databases. Intersection genes of differentially expressed genes (DEGs) between BLCA and control samples in TCGA-BLCA, mitochondrial-related genes (MRGs) and PCD-related genes (PCD-RGs) were obtained for univariate and multivariate Cox regression analysis. Prognostic genes were selected, followed by prognostic model development. The model’s validity was evaluated and validated in GSE32894. To enhance clinical precision, a nomogram was developed combining clinical traits. Furthermore, enrichment analysis, immune infiltration analysis, and drug sensitivity analysis were employed. Finally, prognostic gene expressions were verified in GSE13507, TCGA-BLCA and via Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). Results: Based on above analysis, 5 prognostic genes (POLB, FASN, CASP9, VDAC2, RHOT2) were selected and a prognostic model constructed, which showed strong predictive capability for sample survival in both TCGA-BLCA and GSE32894. Meanwhile, risk scores of BLCA samples in TCGA-BLCA were calculated, and samples divided into high- and low-risk categories by optimal threshold. Further analysis found risk score, stage and age as independent prognostic factors for nomogram construction. Thereafter, we observed pathways (e.g. epithelial-mesenchymal transition, inflammatory response) related to BLCA were markedly enriched in high-risk patients, with suboptimal immunotherapy response in these patients. Importantly, expression trends of FASN, VDAC2, RHOT2 in BLCA vs control group within TCGA-BLCA, GSE13507, and clinical samples were consistent and significant. Conclusion: In this study, a novel BLCA prognostic model was constructed based on POLB, FASN, CASP9, VDAC2, RHOT2, providing preliminary references for BLCA prognostic evaluation and subsequent diagnosis-treatment related studies.
Keywords: Bladder cancer, programmed cell death, prognosis, Immune infiltration, mitochondrial
Received: 20 Apr 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Zhao, Liu, Wang, Guo and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bin Yang, yangbin19982008@163.com
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