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

Nan Jiang; Chuying Wang; Bingqing Xie; Huangfan Xie; Anguo Wu; Xi Kong; Long Gu; Yong Jiang; Jianhua Peng

Neurobiology of Disease (Sep 2024)

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

Nan Jiang,
Chuying Wang,
Bingqing Xie,
Huangfan Xie,
Anguo Wu,
Xi Kong,
Long Gu,
Yong Jiang,
Jianhua Peng

Affiliations

Nan Jiang: Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Institute of Brain Science, Southwest Medical University, Luzhou, China
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: Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Institute of Brain Science, Southwest Medical University, Luzhou, China
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: Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Key Laboratory of Medical Electrophysiology of Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, 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: Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Institute of Brain Science, Southwest Medical University, Luzhou, China
Yong Jiang: Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Institute of Brain Science, Southwest Medical University, Luzhou, China; Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Corresponding authors at: Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, NO.25 of Taiping Street, Luzhou, Sichuan 646000, China.
Jianhua Peng: Institute of Brain Science, Southwest Medical University, Luzhou, China; Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Sichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Corresponding authors at: Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, NO.25 of Taiping Street, Luzhou, Sichuan 646000, China.

Journal volume & issue: Vol. 199
p. 106583

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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