Immune perturbation network identifies an EMT subtype with chromosomal instability and tumor immune-desert microenvironment

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

doi:10.1016/j.isci.2023.107871

Immune perturbation network identifies an EMT subtype with chromosomal instability and tumor immune-desert microenvironment

iScience. 2023 Sep 9;26(10):107871. doi: 10.1016/j.isci.2023.107871. eCollection 2023 Oct 20.

Authors

Hui Xu¹, Xinyu Fu², Ben Liu³, Siyuan Weng¹, Chunguang Guo⁴, Libo Quan⁵, Long Liu⁶, Libo Wang⁶, Zhe Xing⁷, Quan Cheng⁸, Peng Luo⁹, Kexin Chen³, Zaoqu Liu^{10

11}, Xinwei Han¹

Affiliations

¹ Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
² Genetic and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Key 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.
⁴ Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
⁵ Department of Gastroenterology and Hepatology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
⁶ Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
⁷ Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁸ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
⁹ Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
¹⁰ State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
¹¹ 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.

Abstract

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.

Keywords: Genomic analysis; Immunology; Oncology; Transcriptomics.