Disulfide bond-related gene signature development for bladder cancer prognosis prediction and immune microenvironment characterization
Abstract Bladder cancer is the fourth most common malignant tumor in men, with limited therapeutic biomarkers and heterogeneous responses to immunotherapy. Disulfide bond-driven cell death has emerged as a critical regulator of tumor progression and immune microenvironment remodeling. By integrating...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-03974-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850231459549282304 |
|---|---|
| author | Hua Huang Haiyan Shao Yifan Wang Lili Ge |
| author_facet | Hua Huang Haiyan Shao Yifan Wang Lili Ge |
| author_sort | Hua Huang |
| collection | DOAJ |
| description | Abstract Bladder cancer is the fourth most common malignant tumor in men, with limited therapeutic biomarkers and heterogeneous responses to immunotherapy. Disulfide bond-driven cell death has emerged as a critical regulator of tumor progression and immune microenvironment remodeling. By integrating data from TCGA and GEO cohorts, we developed a Disulfide-Related Prognostic Signature (DRPS) using ten machine learning algorithms. Single-cell RNA sequencing (scRNA-seq) elucidated the cell subtype-specific expression patterns of disulfide bond regulatory genes, while immune microenvironment and drug sensitivity analyses validated its clinical translational potential. qRT-PCR experiments confirmed differential expression patterns of core genes in bladder cancer cell lines. The DRPS model, optimized by the StepCox[backward] algorithm, demonstrated robust prognostic accuracy across four validation cohorts (mean C-index = 0.658). High-risk patients exhibited an enhanced immunosuppressive microenvironment characterized by infiltrated activated cancer-associated fibroblasts, upregulated APC co-inhibition pathways, and elevated immune checkpoint expression. Notably, high DRPS scores were associated with primary resistance to immunotherapy but showed increased sensitivity to anti-tumor agents such as Elephantine and Leflunomide. This study establishes a novel DRPS that serves as a predictive indicator for bladder cancer prognosis and pan-cancer immunotherapy efficacy. |
| format | Article |
| id | doaj-art-1da7f7ae60ed4d34b3d82c128663a334 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-1da7f7ae60ed4d34b3d82c128663a3342025-08-20T02:03:31ZengNature PortfolioScientific Reports2045-23222025-05-0115111210.1038/s41598-025-03974-wDisulfide bond-related gene signature development for bladder cancer prognosis prediction and immune microenvironment characterizationHua Huang0Haiyan Shao1Yifan Wang2Lili Ge3 Department of Urology, Urology and Nephrology Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College Department of Urology, Urology and Nephrology Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College Department of Urology, Urology and Nephrology Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeDepartment of Nursing, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeAbstract Bladder cancer is the fourth most common malignant tumor in men, with limited therapeutic biomarkers and heterogeneous responses to immunotherapy. Disulfide bond-driven cell death has emerged as a critical regulator of tumor progression and immune microenvironment remodeling. By integrating data from TCGA and GEO cohorts, we developed a Disulfide-Related Prognostic Signature (DRPS) using ten machine learning algorithms. Single-cell RNA sequencing (scRNA-seq) elucidated the cell subtype-specific expression patterns of disulfide bond regulatory genes, while immune microenvironment and drug sensitivity analyses validated its clinical translational potential. qRT-PCR experiments confirmed differential expression patterns of core genes in bladder cancer cell lines. The DRPS model, optimized by the StepCox[backward] algorithm, demonstrated robust prognostic accuracy across four validation cohorts (mean C-index = 0.658). High-risk patients exhibited an enhanced immunosuppressive microenvironment characterized by infiltrated activated cancer-associated fibroblasts, upregulated APC co-inhibition pathways, and elevated immune checkpoint expression. Notably, high DRPS scores were associated with primary resistance to immunotherapy but showed increased sensitivity to anti-tumor agents such as Elephantine and Leflunomide. This study establishes a novel DRPS that serves as a predictive indicator for bladder cancer prognosis and pan-cancer immunotherapy efficacy.https://doi.org/10.1038/s41598-025-03974-wBladder cancerDisulfide bondsMachine learningPrognostic signatureImmunotherapy |
| spellingShingle | Hua Huang Haiyan Shao Yifan Wang Lili Ge Disulfide bond-related gene signature development for bladder cancer prognosis prediction and immune microenvironment characterization Scientific Reports Bladder cancer Disulfide bonds Machine learning Prognostic signature Immunotherapy |
| title | Disulfide bond-related gene signature development for bladder cancer prognosis prediction and immune microenvironment characterization |
| title_full | Disulfide bond-related gene signature development for bladder cancer prognosis prediction and immune microenvironment characterization |
| title_fullStr | Disulfide bond-related gene signature development for bladder cancer prognosis prediction and immune microenvironment characterization |
| title_full_unstemmed | Disulfide bond-related gene signature development for bladder cancer prognosis prediction and immune microenvironment characterization |
| title_short | Disulfide bond-related gene signature development for bladder cancer prognosis prediction and immune microenvironment characterization |
| title_sort | disulfide bond related gene signature development for bladder cancer prognosis prediction and immune microenvironment characterization |
| topic | Bladder cancer Disulfide bonds Machine learning Prognostic signature Immunotherapy |
| url | https://doi.org/10.1038/s41598-025-03974-w |
| work_keys_str_mv | AT huahuang disulfidebondrelatedgenesignaturedevelopmentforbladdercancerprognosispredictionandimmunemicroenvironmentcharacterization AT haiyanshao disulfidebondrelatedgenesignaturedevelopmentforbladdercancerprognosispredictionandimmunemicroenvironmentcharacterization AT yifanwang disulfidebondrelatedgenesignaturedevelopmentforbladdercancerprognosispredictionandimmunemicroenvironmentcharacterization AT lilige disulfidebondrelatedgenesignaturedevelopmentforbladdercancerprognosispredictionandimmunemicroenvironmentcharacterization |