An oncogene regulating chromatin favors response to immunotherapy<subtitle>Oncogene CHAF1A and immunotherapy outcomes</subtitle>
Many biological processes related to cell function and fate begin with chromatin alterations, and many factors associated with the efficacy of immune checkpoint inhibitors (ICIs) are actually downstream events of chromatin alterations, such as genome changes, neoantigen production, and immune checkp...
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| Format: | Article |
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2303195 |
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| author | Leqian Ying Zhangmin Hu Yi Lu Qing Tao Fen Xiong Yongqian Shu Yufei Yang Xuehan Qiao Chen Peng Yuchun Jiang Miao Han Min Xu Xiaoqin Li Deqiang Wang |
| author_facet | Leqian Ying Zhangmin Hu Yi Lu Qing Tao Fen Xiong Yongqian Shu Yufei Yang Xuehan Qiao Chen Peng Yuchun Jiang Miao Han Min Xu Xiaoqin Li Deqiang Wang |
| author_sort | Leqian Ying |
| collection | DOAJ |
| description | Many biological processes related to cell function and fate begin with chromatin alterations, and many factors associated with the efficacy of immune checkpoint inhibitors (ICIs) are actually downstream events of chromatin alterations, such as genome changes, neoantigen production, and immune checkpoint expression. However, the influence of genes as chromatin regulators on the efficacy of ICIs remains elusive, especially in gastric cancer (GC). In this study, thirty out of 1593 genes regulating chromatin associated with a favorable prognosis were selected for GC. CHAF1A, a well-defined oncogene, was identified as the highest linkage hub gene. High CHAF1A expression were associated with microsatellite instability (MSI), high tumor mutation burden (TMB), high tumor neoantigen burden (TNB), high expressions of PD-L1 and immune effector genes, and live infiltration of immune cells. High CHAF1A expression indicated a favorable response and prognosis in immunotherapy of several cohorts, which was independent of MSI, TMB, TNB, PD-L1 expression, immune phenotype and transcriptome scoring, and improved patient selection based on these classic biomarkers. In vivo, CHAF1A knockdown alone inhibited tumor growth but it impaired the effect of an anti-PD-1 antibody by increasing the relative tumor proliferation rate and decreasing the survival benefit, potentially through the activation of TGF-β signaling. In conclusion, CHAF1A may be a novel biomarker for improving patient selection in immunotherapy. |
| format | Article |
| id | doaj-art-02e0a98dc2074dc6b0eb068f73333cfd |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-02e0a98dc2074dc6b0eb068f73333cfd2024-12-03T13:49:34ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2303195An oncogene regulating chromatin favors response to immunotherapy<subtitle>Oncogene CHAF1A and immunotherapy outcomes</subtitle>Leqian Ying0Zhangmin Hu1Yi Lu2Qing Tao3Fen Xiong4Yongqian Shu5Yufei Yang6Xuehan Qiao7Chen Peng8Yuchun Jiang9Miao Han10Min Xu11Xiaoqin Li12Deqiang Wang13Department of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Oncology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, ChinaDepartment of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Oncology, Jiangsu Province Hospital & The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Gastroenterology, Digestive Disease Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaMany biological processes related to cell function and fate begin with chromatin alterations, and many factors associated with the efficacy of immune checkpoint inhibitors (ICIs) are actually downstream events of chromatin alterations, such as genome changes, neoantigen production, and immune checkpoint expression. However, the influence of genes as chromatin regulators on the efficacy of ICIs remains elusive, especially in gastric cancer (GC). In this study, thirty out of 1593 genes regulating chromatin associated with a favorable prognosis were selected for GC. CHAF1A, a well-defined oncogene, was identified as the highest linkage hub gene. High CHAF1A expression were associated with microsatellite instability (MSI), high tumor mutation burden (TMB), high tumor neoantigen burden (TNB), high expressions of PD-L1 and immune effector genes, and live infiltration of immune cells. High CHAF1A expression indicated a favorable response and prognosis in immunotherapy of several cohorts, which was independent of MSI, TMB, TNB, PD-L1 expression, immune phenotype and transcriptome scoring, and improved patient selection based on these classic biomarkers. In vivo, CHAF1A knockdown alone inhibited tumor growth but it impaired the effect of an anti-PD-1 antibody by increasing the relative tumor proliferation rate and decreasing the survival benefit, potentially through the activation of TGF-β signaling. In conclusion, CHAF1A may be a novel biomarker for improving patient selection in immunotherapy.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2303195CancerCHAF1Aimmune checkpointimmunotherapyoncogene |
| spellingShingle | Leqian Ying Zhangmin Hu Yi Lu Qing Tao Fen Xiong Yongqian Shu Yufei Yang Xuehan Qiao Chen Peng Yuchun Jiang Miao Han Min Xu Xiaoqin Li Deqiang Wang An oncogene regulating chromatin favors response to immunotherapy<subtitle>Oncogene CHAF1A and immunotherapy outcomes</subtitle> OncoImmunology Cancer CHAF1A immune checkpoint immunotherapy oncogene |
| title | An oncogene regulating chromatin favors response to immunotherapy<subtitle>Oncogene CHAF1A and immunotherapy outcomes</subtitle> |
| title_full | An oncogene regulating chromatin favors response to immunotherapy<subtitle>Oncogene CHAF1A and immunotherapy outcomes</subtitle> |
| title_fullStr | An oncogene regulating chromatin favors response to immunotherapy<subtitle>Oncogene CHAF1A and immunotherapy outcomes</subtitle> |
| title_full_unstemmed | An oncogene regulating chromatin favors response to immunotherapy<subtitle>Oncogene CHAF1A and immunotherapy outcomes</subtitle> |
| title_short | An oncogene regulating chromatin favors response to immunotherapy<subtitle>Oncogene CHAF1A and immunotherapy outcomes</subtitle> |
| title_sort | oncogene regulating chromatin favors response to immunotherapy subtitle oncogene chaf1a and immunotherapy outcomes subtitle |
| topic | Cancer CHAF1A immune checkpoint immunotherapy oncogene |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2303195 |
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