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An oncogene regulating chromatin favors response to immunotherapy: Oncogene CHAF1A and immunotherapy outcomes.
Ying, Leqian; Hu, Zhangmin; Lu, Yi; Tao, Qing; Xiong, Fen; Shu, Yongqian; Yang, Yufei; Qiao, Xuehan; Peng, Chen; Jiang, Yuchun; Han, Miao; Xu, Min; Li, Xiaoqin; Wang, Deqiang.
Afiliación
  • Ying L; Department of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • Hu Z; Department of Oncology, Zhong-Da Hospital, Medicine School, Southeast University, Nanjing, China.
  • Lu Y; Department of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • Tao Q; Department of Oncology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China.
  • Xiong F; Department of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • Shu Y; Department of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • Yang Y; Department of Oncology, Jiangsu Province Hospital & The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • Qiao X; Department of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • Peng C; Department of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • Jiang Y; Department of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • Han M; Department of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • Xu M; Department of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • Li X; Department of Gastroenterology, Digestive Disease Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • Wang D; Department of Oncology, Digestive Disease Institute&Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Oncoimmunology ; 13(1): 2303195, 2024.
Article en En | MEDLINE | ID: mdl-38235318
ABSTRACT
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-ß signaling. In conclusion, CHAF1A may be a novel biomarker for improving patient selection in immunotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Antígeno B7-H1 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Oncoimmunology Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Antígeno B7-H1 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Oncoimmunology Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos