Identification of endoplasmic reticulum stress genes in human stroke based on bioinformatics and machine learning.

Journal: Neurobiology of disease
PMID: 38942324

Abstract

After ischemic stroke (IS), secondary injury is intimately linked to endoplasmic reticulum (ER) stress and body-brain crosstalk. Nonetheless, the underlying mechanism systemic immune disorder mediated ER stress in human IS remains unknown. In this study, 32 candidate ER stress-related genes (ERSRGs) were identified by overlapping MSigDB ER stress pathway genes and DEGs. Three Key ERSRGs (ATF6, DDIT3 and ERP29) were identified using LASSO, random forest, and SVM-RFE. IS patients with different ERSRGs profile were clustered into two groups using consensus clustering and the difference between 2 group was further explored by GSVA. Through immune cell infiltration deconvolution analysis, and middle cerebral artery occlusion (MCAO) mouse scRNA analysis, we found that the expression of 3 key ERSRGs were closely related with peripheral macrophage cell ER stress in IS and this was further confirmed by RT-qPCR experiment. These ERS genes might be helpful to further accurately regulate the central nervous system and systemic immune response through ER stress and have potential application value in clinical practice in IS.

Authors

  • Nan Jiang
  • Chuying Wang
    Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, China.
  • Bingqing Xie
    Department of Human Genetics, University of Chicago, 920 E. 58th Street, Chicago, IL 60637, USA Department of Computer Science, Illinois Institute of Technology, Chicago, IL 60616, USA.
  • Huangfan Xie
    Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Institute of Brain Science, Southwest Medical University, Luzhou, China.
  • Anguo Wu
    Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
  • Xi Kong
    Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Institute of Brain Science, Southwest Medical University, Luzhou, China.
  • Long Gu
    School of Nuclear Science and Technology, Lanzhou University, Lanzhou, China.
  • Yong Jiang
    Department of Pathology West China Hospital Sichuan University Chengdu China.
  • Jianhua Peng
    Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan 430056, China.

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