Immune perturbation network identifies an EMT subtype with chromosomal instability and tumor immune-desert microenvironment
Summary: Most gastric cancer (GC) subtypes are identified through transcriptional profiling overlooking dynamic changes and interactions in gene expression. Based on the background network of global immune genes, we constructed sample-specific edge-perturbation matrices and identified four molecular...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422301948X |
| _version_ | 1797647796657979392 |
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| author | Hui Xu Xinyu Fu Ben Liu Siyuan Weng Chunguang Guo Libo Quan Long Liu Libo Wang Zhe Xing Quan Cheng Peng Luo Kexin Chen Zaoqu Liu Xinwei Han |
| author_facet | Hui Xu Xinyu Fu Ben Liu Siyuan Weng Chunguang Guo Libo Quan Long Liu Libo Wang Zhe Xing Quan Cheng Peng Luo Kexin Chen Zaoqu Liu Xinwei Han |
| author_sort | Hui Xu |
| collection | DOAJ |
| description | Summary: Most gastric cancer (GC) subtypes are identified through transcriptional profiling overlooking dynamic changes and interactions in gene expression. Based on the background network of global immune genes, we constructed sample-specific edge-perturbation matrices and identified four molecular network subtypes of GC (MNG). MNG-1 displayed the best prognosis and vigorous cell cycle activity. MNG-2 was enriched by immune-hot phenotype with the potential for immunotherapy response. MNG-3 and MNG-4 were identified with epithelial-mesenchymal transition (EMT) peculiarity and worse prognosis, termed EMT subtypes. MNG-3 was characterized by low mutational burden and stromal cells and considered a replica of previous subtypes associated with poor prognosis. Notably, MNG-4 was considered a previously undefined subtype with a dismal prognosis, characterized by chromosomal instability and immune-desert microenvironment. This subtype tended to metastasize and was resistant to respond to immunotherapy. Pharmacogenomics analysis showed three therapeutic agents (NVP-BEZ235, LY2606368, and rutin) were potential interventions for MNG-4. |
| first_indexed | 2024-03-11T15:22:46Z |
| format | Article |
| id | doaj.art-07614151b430411b9451ca925349266a |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T15:22:46Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-07614151b430411b9451ca925349266a2023-10-28T05:08:49ZengElsevieriScience2589-00422023-10-012610107871Immune perturbation network identifies an EMT subtype with chromosomal instability and tumor immune-desert microenvironmentHui Xu0Xinyu Fu1Ben Liu2Siyuan Weng3Chunguang Guo4Libo Quan5Long Liu6Libo Wang7Zhe Xing8Quan Cheng9Peng Luo10Kexin Chen11Zaoqu Liu12Xinwei Han13Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, ChinaGenetic and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Molecular Cancer Epidemiology of Tianjin, Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, ChinaDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, ChinaDepartment of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, ChinaDepartment of Gastroenterology and Hepatology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaKey Laboratory of Molecular Cancer Epidemiology of Tianjin, Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; Corresponding authorState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China; State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, 100730, China; Corresponding authorDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Corresponding authorSummary: Most gastric cancer (GC) subtypes are identified through transcriptional profiling overlooking dynamic changes and interactions in gene expression. Based on the background network of global immune genes, we constructed sample-specific edge-perturbation matrices and identified four molecular network subtypes of GC (MNG). MNG-1 displayed the best prognosis and vigorous cell cycle activity. MNG-2 was enriched by immune-hot phenotype with the potential for immunotherapy response. MNG-3 and MNG-4 were identified with epithelial-mesenchymal transition (EMT) peculiarity and worse prognosis, termed EMT subtypes. MNG-3 was characterized by low mutational burden and stromal cells and considered a replica of previous subtypes associated with poor prognosis. Notably, MNG-4 was considered a previously undefined subtype with a dismal prognosis, characterized by chromosomal instability and immune-desert microenvironment. This subtype tended to metastasize and was resistant to respond to immunotherapy. Pharmacogenomics analysis showed three therapeutic agents (NVP-BEZ235, LY2606368, and rutin) were potential interventions for MNG-4.http://www.sciencedirect.com/science/article/pii/S258900422301948XOncologyImmunologyGenomic analysisTranscriptomics |
| spellingShingle | Hui Xu Xinyu Fu Ben Liu Siyuan Weng Chunguang Guo Libo Quan Long Liu Libo Wang Zhe Xing Quan Cheng Peng Luo Kexin Chen Zaoqu Liu Xinwei Han Immune perturbation network identifies an EMT subtype with chromosomal instability and tumor immune-desert microenvironment iScience Oncology Immunology Genomic analysis Transcriptomics |
| title | Immune perturbation network identifies an EMT subtype with chromosomal instability and tumor immune-desert microenvironment |
| title_full | Immune perturbation network identifies an EMT subtype with chromosomal instability and tumor immune-desert microenvironment |
| title_fullStr | Immune perturbation network identifies an EMT subtype with chromosomal instability and tumor immune-desert microenvironment |
| title_full_unstemmed | Immune perturbation network identifies an EMT subtype with chromosomal instability and tumor immune-desert microenvironment |
| title_short | Immune perturbation network identifies an EMT subtype with chromosomal instability and tumor immune-desert microenvironment |
| title_sort | immune perturbation network identifies an emt subtype with chromosomal instability and tumor immune desert microenvironment |
| topic | Oncology Immunology Genomic analysis Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S258900422301948X |
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