DAMPs prognostic signature predicts tumor immunotherapy, and identifies immunosuppressive mechanism of pannexin 1 channels in pancreatic ductal adenocarcinoma
BackgroundDamage-associated molecular patterns (DAMPs) induced by immunogenic cell death (ICD) may be useful for the immunotherapy to patients undergoing pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to predict the prognosis and immunotherapy responsiveness of PDAC patients using...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1516457/full |
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| author | Qianxue Wu Qian Xiao Qian Xiao Xin Tang Liuying Li Daqiang Song Yang Zhou Benhua Li Benhua Li Guosheng Ren Guosheng Ren Fang Luo |
| author_facet | Qianxue Wu Qian Xiao Qian Xiao Xin Tang Liuying Li Daqiang Song Yang Zhou Benhua Li Benhua Li Guosheng Ren Guosheng Ren Fang Luo |
| author_sort | Qianxue Wu |
| collection | DOAJ |
| description | BackgroundDamage-associated molecular patterns (DAMPs) induced by immunogenic cell death (ICD) may be useful for the immunotherapy to patients undergoing pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to predict the prognosis and immunotherapy responsiveness of PDAC patients using DAMPs-related genes.MethodsK-means analysis was used to identify the DAMPs-related subtypes of 175 PDAC cases. The significance of gene mutation and immune status in different subtypes was detected. LASSO regression was used to construct a DAMPs-related prognostic signature to predict the immunotherapy responsiveness of PDAC. Subsequently, in vivo and in vitro experiments and Bulk-RNA seq were used to verify the effect of hub gene pannexin 1 (PANX1) on PDAC.ResultsTwo subtypes were clustered based on the expression levels of DAMPs genes from 175 PDAC patients. Besides, the prognosis and immune landscape in up-regulated DAMPs expression subtypes was poor. In addition, we constructed a DAMPs-related prognostic signature that correlated with immune cell infiltration and predicted immunotherapy or chemotherapy responsiveness of patients with PDAC. Mechanically, through Bulk-RNA sequencing and experiments, we found that PANX1 promoted tumor progression and immune regulation via the ATP release to active NOD1/NFκB signaling pathway in PDAC.ConclusionOur in silico analyses established a classification system based on ICD-related DAMPs genes in PDAC, and constructed a DAMPs-related prognostic model to predict the efficacy of immunotherapy. This study will provide a new perspective for targeting the DAMPs-related molecule PANX1 in the treatment of PDAC. |
| format | Article |
| id | doaj-art-f07ec22cb86b41ce8364aef60d3fca08 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-f07ec22cb86b41ce8364aef60d3fca082025-01-15T11:49:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15164571516457DAMPs prognostic signature predicts tumor immunotherapy, and identifies immunosuppressive mechanism of pannexin 1 channels in pancreatic ductal adenocarcinomaQianxue Wu0Qian Xiao1Qian Xiao2Xin Tang3Liuying Li4Daqiang Song5Yang Zhou6Benhua Li7Benhua Li8Guosheng Ren9Guosheng Ren10Fang Luo11Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Breast and Thyroid Surgery, Women and Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Respiratory and Critical Care Medicine, The First People’s Hospital of Chongqing Liang Jiang New Area, Chongqing, ChinaChongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Clinical Laboratory, The Second People’ s Hospital of Liangshan yi Autonomous Prefecture, Xichang, ChinaClinical Molecular Medicine Testing Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaBackgroundDamage-associated molecular patterns (DAMPs) induced by immunogenic cell death (ICD) may be useful for the immunotherapy to patients undergoing pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to predict the prognosis and immunotherapy responsiveness of PDAC patients using DAMPs-related genes.MethodsK-means analysis was used to identify the DAMPs-related subtypes of 175 PDAC cases. The significance of gene mutation and immune status in different subtypes was detected. LASSO regression was used to construct a DAMPs-related prognostic signature to predict the immunotherapy responsiveness of PDAC. Subsequently, in vivo and in vitro experiments and Bulk-RNA seq were used to verify the effect of hub gene pannexin 1 (PANX1) on PDAC.ResultsTwo subtypes were clustered based on the expression levels of DAMPs genes from 175 PDAC patients. Besides, the prognosis and immune landscape in up-regulated DAMPs expression subtypes was poor. In addition, we constructed a DAMPs-related prognostic signature that correlated with immune cell infiltration and predicted immunotherapy or chemotherapy responsiveness of patients with PDAC. Mechanically, through Bulk-RNA sequencing and experiments, we found that PANX1 promoted tumor progression and immune regulation via the ATP release to active NOD1/NFκB signaling pathway in PDAC.ConclusionOur in silico analyses established a classification system based on ICD-related DAMPs genes in PDAC, and constructed a DAMPs-related prognostic model to predict the efficacy of immunotherapy. This study will provide a new perspective for targeting the DAMPs-related molecule PANX1 in the treatment of PDAC.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1516457/fullPANX1DAMPsPDACNOD1NFκB |
| spellingShingle | Qianxue Wu Qian Xiao Qian Xiao Xin Tang Liuying Li Daqiang Song Yang Zhou Benhua Li Benhua Li Guosheng Ren Guosheng Ren Fang Luo DAMPs prognostic signature predicts tumor immunotherapy, and identifies immunosuppressive mechanism of pannexin 1 channels in pancreatic ductal adenocarcinoma Frontiers in Immunology PANX1 DAMPs PDAC NOD1 NFκB |
| title | DAMPs prognostic signature predicts tumor immunotherapy, and identifies immunosuppressive mechanism of pannexin 1 channels in pancreatic ductal adenocarcinoma |
| title_full | DAMPs prognostic signature predicts tumor immunotherapy, and identifies immunosuppressive mechanism of pannexin 1 channels in pancreatic ductal adenocarcinoma |
| title_fullStr | DAMPs prognostic signature predicts tumor immunotherapy, and identifies immunosuppressive mechanism of pannexin 1 channels in pancreatic ductal adenocarcinoma |
| title_full_unstemmed | DAMPs prognostic signature predicts tumor immunotherapy, and identifies immunosuppressive mechanism of pannexin 1 channels in pancreatic ductal adenocarcinoma |
| title_short | DAMPs prognostic signature predicts tumor immunotherapy, and identifies immunosuppressive mechanism of pannexin 1 channels in pancreatic ductal adenocarcinoma |
| title_sort | damps prognostic signature predicts tumor immunotherapy and identifies immunosuppressive mechanism of pannexin 1 channels in pancreatic ductal adenocarcinoma |
| topic | PANX1 DAMPs PDAC NOD1 NFκB |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1516457/full |
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