Affiliation:
1. Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Joint Innovation
Center for Brain Disorders, Capital Medical University, Beijing, China
2. Department of Surgery, Stanford University
School of Medicine, Stanford, CA 94305, USA
3. The Second Hospital of Jiaxing, The Second Affiliated Hospital of
Jiaxing University, Jiaxing, China
Abstract
Background:
Stroke-Induced Immunodepression (SIID) is characterized by apoptosis
in blood immune populations, such as T cells, B cells, NK cells, and monocytes, leading to the
clinical presentation of lymphopenia. Disulfidptosis is a novel form of programmed cell death
characterized by accumulating disulfide bonds in the cytoplasm, resulting in cellular dysfunction
and eventual cell death.
Objective:
In this study, we investigated the association between disulfidptosis and stroke by
analyzing gene sequencing data from peripheral blood samples of stroke patients.
Methods:
Differential gene expression analysis identified a set of disulfidptosis-related genes
(DRGs) significantly associated with stroke. Initial exploration identified 32 DRGs and their
interactions. Our study encompassed several analyses to understand the molecular mechanisms
of DRGs in stroke. Weighted Gene Co-Expression Network Analysis (WGCNA) uncovered
modules of co-expressed genes in stroke samples, and differentially expressed gene (DEG) analysis
highlighted 1643 key genes.
Results:
These analyses converged on four hub genes of DRGs (SLC2A3, SLC2A14, SLC7A11,
NCKAP1) associated with stroke. Immune cell composition analysis indicated positive correlations
between hub genes and macrophages M1, M2, and neutrophils and negative associations
with CD4+ and CD8+ T cells, B cells, and NK cells. Sub-cluster analysis revealed two distinct
clusters with different immune cell expression profiles. Gene Set Enrichment Analysis (GSEA)
demonstrated enrichment of apoptosis-related pathways, neurotrophin signaling, and actin cytoskeleton
regulation. Associations between hub genes and apoptosis, necroptosis, ferroptosis, and
cuproptosis, were also identified.
Conclusion:
These results suggest that the DRG hub genes are interconnected with various cell
death pathways and immune processes, potentially contributing to stroke pathological development.
Funder
Medical and Health Science and Technology Project of Zhejiang Province
Zhejiang Basic Public Welfare Research Program
Publisher
Bentham Science Publishers Ltd.