Prognostic and immunotherapeutic potential of disulfidptosis-associated signature in pancreatic cancer
Disulfidptosis is a newly discovered formation of programmed cell death. However, the significance of disulfidptosis in pancreatic adenocarcinoma remains unclear. Our investigation aims to elucidate the significance of disulfidptosis in pancreatic ductal adenocarcinoma by integrating diverse dataset...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568976/full |
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| author | Ran Cui Gaoming Wang Renhao Hu Yongkun Wang Huiling Mu Yanxiang Song Bo Chen Xiaohua Jiang |
| author_facet | Ran Cui Gaoming Wang Renhao Hu Yongkun Wang Huiling Mu Yanxiang Song Bo Chen Xiaohua Jiang |
| author_sort | Ran Cui |
| collection | DOAJ |
| description | Disulfidptosis is a newly discovered formation of programmed cell death. However, the significance of disulfidptosis in pancreatic adenocarcinoma remains unclear. Our investigation aims to elucidate the significance of disulfidptosis in pancreatic ductal adenocarcinoma by integrating diverse datasets, including bulk RNA sequencing data, microarray profiles, single-cell transcriptome profiles, spatial transcriptome data, and biospecimens. Utilizing various bioinformatics tools, we screened disulfidptosis-related genes based on single-cell RNA sequencing profiles, subsequently validating them through enrichment analysis. An 8-gene disulfidptosis-related prognostic signature was established by constructing massive LASSO-Cox regression models and validated by multiple external PDAC cohorts. Evaluation methods, such as Kaplan-Meier curves, ROC curves, time-dependent ROC curves, and decision curve analysis, were employed to assess the prognostic signature’s reliability. High disulfidptosis-related scores were associated with a poorer prognosis and diminished sensitivity to immune checkpoint blockade. Further investigation uncovered that the potential components of elevated DPS involve malignant tumor hallmarks, extensive interactions between myCAFs and tumor cells, and the exclusion of immune cells. Cell-cell communication analysis highlighted myCAFs’ role in signaling, potentially influencing tumor cells towards increased malignancy through collagen, laminin, and FN1 signaling networks. Spatial transcriptome analysis confirmed the crosstalk between myCAFs and tumor cells. Biospecimens including 20 pairs of PDAC samples and adjacent normal tissues further demonstrated the robustness of DPS and its correlation with CAF markers. In conclusion, our study introduces a novel disulfidptosis-related signature with high efficacy in patient risk stratification, which has the ability to predict the sensitivity to immune checkpoint blockade. |
| format | Article |
| id | doaj-art-8fb29323bff247c8b1fd1eb58f253d70 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-8fb29323bff247c8b1fd1eb58f253d702025-08-20T02:40:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15689761568976Prognostic and immunotherapeutic potential of disulfidptosis-associated signature in pancreatic cancerRan Cui0Gaoming Wang1Renhao Hu2Yongkun Wang3Huiling Mu4Yanxiang Song5Bo Chen6Xiaohua Jiang7Department of Hepatopancreatobiliary Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Hepatopancreatobiliary Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Hepatopancreatobiliary Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Biobank, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Biobank, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Hepatopancreatobiliary Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Hepatopancreatobiliary Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDisulfidptosis is a newly discovered formation of programmed cell death. However, the significance of disulfidptosis in pancreatic adenocarcinoma remains unclear. Our investigation aims to elucidate the significance of disulfidptosis in pancreatic ductal adenocarcinoma by integrating diverse datasets, including bulk RNA sequencing data, microarray profiles, single-cell transcriptome profiles, spatial transcriptome data, and biospecimens. Utilizing various bioinformatics tools, we screened disulfidptosis-related genes based on single-cell RNA sequencing profiles, subsequently validating them through enrichment analysis. An 8-gene disulfidptosis-related prognostic signature was established by constructing massive LASSO-Cox regression models and validated by multiple external PDAC cohorts. Evaluation methods, such as Kaplan-Meier curves, ROC curves, time-dependent ROC curves, and decision curve analysis, were employed to assess the prognostic signature’s reliability. High disulfidptosis-related scores were associated with a poorer prognosis and diminished sensitivity to immune checkpoint blockade. Further investigation uncovered that the potential components of elevated DPS involve malignant tumor hallmarks, extensive interactions between myCAFs and tumor cells, and the exclusion of immune cells. Cell-cell communication analysis highlighted myCAFs’ role in signaling, potentially influencing tumor cells towards increased malignancy through collagen, laminin, and FN1 signaling networks. Spatial transcriptome analysis confirmed the crosstalk between myCAFs and tumor cells. Biospecimens including 20 pairs of PDAC samples and adjacent normal tissues further demonstrated the robustness of DPS and its correlation with CAF markers. In conclusion, our study introduces a novel disulfidptosis-related signature with high efficacy in patient risk stratification, which has the ability to predict the sensitivity to immune checkpoint blockade.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568976/fulldisulfidptosispancreatic adenocarcinomaprognostic signaturetumor microenvironmentimmunotherapy |
| spellingShingle | Ran Cui Gaoming Wang Renhao Hu Yongkun Wang Huiling Mu Yanxiang Song Bo Chen Xiaohua Jiang Prognostic and immunotherapeutic potential of disulfidptosis-associated signature in pancreatic cancer Frontiers in Immunology disulfidptosis pancreatic adenocarcinoma prognostic signature tumor microenvironment immunotherapy |
| title | Prognostic and immunotherapeutic potential of disulfidptosis-associated signature in pancreatic cancer |
| title_full | Prognostic and immunotherapeutic potential of disulfidptosis-associated signature in pancreatic cancer |
| title_fullStr | Prognostic and immunotherapeutic potential of disulfidptosis-associated signature in pancreatic cancer |
| title_full_unstemmed | Prognostic and immunotherapeutic potential of disulfidptosis-associated signature in pancreatic cancer |
| title_short | Prognostic and immunotherapeutic potential of disulfidptosis-associated signature in pancreatic cancer |
| title_sort | prognostic and immunotherapeutic potential of disulfidptosis associated signature in pancreatic cancer |
| topic | disulfidptosis pancreatic adenocarcinoma prognostic signature tumor microenvironment immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568976/full |
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