Liu Shan-Peng, Liu Cuiying, Xu Baohui, Zhou Hongmei, Zhao Heng
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.
Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Curr Neurovasc Res. 2024;20(5):608-622. doi: 10.2174/0115672026286243240105115419.
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.
In this study, we investigated the association between disulfidptosis and stroke by analyzing gene sequencing data from peripheral blood samples of stroke patients.
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.
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.
These results suggest that the DRG hub genes are interconnected with various cell death pathways and immune processes, potentially contributing to stroke pathological development.
卒中诱导的免疫抑制（SIID）的特征是血液免疫细胞群体（如T细胞、B细胞、NK细胞和单核细胞）发生凋亡，导致淋巴细胞减少的临床表现。二硫键介导的细胞死亡是一种新型程序性细胞死亡形式，其特征是细胞质中二硫键积累，导致细胞功能障碍并最终导致细胞死亡。
在本研究中，我们通过分析卒中患者外周血样本的基因测序数据，研究二硫键介导的细胞死亡与卒中之间的关联。
差异基因表达分析确定了一组与卒中显著相关的二硫键介导的细胞死亡相关基因（DRGs）。初步探索确定了32个DRGs及其相互作用。我们的研究包括多项分析，以了解DRGs在卒中中的分子机制。加权基因共表达网络分析（WGCNA）揭示了卒中样本中共表达基因的模块，差异表达基因（DEG）分析突出了1643个关键基因。
这些分析聚焦于与卒中相关的四个DRG核心基因（SLC2A3、SLC2A14、SLC7A11、NCKAP1）。免疫细胞组成分析表明，核心基因与巨噬细胞M1、M2和中性粒细胞呈正相关，与CD4+和CD8+T细胞、B细胞和NK细胞呈负相关。亚聚类分析揭示了两个具有不同免疫细胞表达谱的不同聚类。基因集富集分析（GSEA）表明凋亡相关通路、神经营养因子信号传导和肌动蛋白细胞骨架调节富集。还确定了核心基因与凋亡、坏死性凋亡、铁死亡和铜死亡之间的关联。
这些结果表明，DRG核心基因与各种细胞死亡途径和免疫过程相互关联，可能有助于卒中的病理发展。
Zotero 插件