Disulfidptosis and its Role in Peripheral Blood Immune Cells after a Stroke: A New Frontier in Stroke Pathogenesis

Shan-Peng Liu; Cuiying Liu; Baohui Xu; Hongmei Zhou; Heng Zhao

doi:10.2174/0115672026286243240105115419

Disulfidptosis and its Role in Peripheral Blood Immune Cells after a Stroke: A New Frontier in Stroke Pathogenesis

Curr Neurovasc Res. 2024 Jan 30. doi: 10.2174/0115672026286243240105115419. Online ahead of print.

Authors

Shan-Peng Liu¹, Cuiying Liu¹, Baohui Xu², Hongmei Zhou³, Heng Zhao¹

Affiliations

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.

PMID: 38299279
DOI: 10.2174/0115672026286243240105115419

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.

Keywords: GEO; WGCNA; bioinformatics; disulfidptosis; programmed cell death; stroke.