Li Tianzhi, Kang Xiaojia, Zhang Sijie, Wang Yihan, He Jinshan, Li Hongyan, Shao Chen, Kang Jingsong
Department of Pathophysiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basical Medical Sciences, Jilin University, Changchun, China.
Front Immunol. 2025 Mar 26;16:1561544. doi: 10.3389/fimmu.2025.1561544. eCollection 2025.
Ischemic stroke (IS) is a major global cause of death and disability, linked to nucleotide metabolism imbalances. This study aimed to identify nucleotide metabolism-related genes associated with IS and explore their roles in disease mechanisms for new diagnostic and therapeutic strategies.
IS gene expression data were sourced from the GEO database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted in R, intersecting results with nucleotide metabolism-related genes. Functional enrichment and connectivity map (cMAP) analyses identified key genes and potential therapeutic agents. Core immune-related genes were determined using LASSO regression, SVM-RFE, and Random Forest algorithms. Immune cell infiltration levels and correlations were analyzed via CIBERSORT. Single-cell RNA sequencing (scRNA-seq) data and molecular docking assessed gene expression, localization, and gene-drug binding. experiments validated core gene expression.
Thirty-three candidate genes were identified, mainly involved in immune and inflammatory responses. , and emerged as key immune-related genes, linked to immune cell infiltration and showing high diagnostic potential. cMAP analysis indicated these genes as drug targets. scRNA-seq clarified their expression and localization, and molecular docking confirmed strong drug binding. experiments validated their significant expression in IS.
This study underscores the role of nucleotide metabolism in IS, identifying , and as potential biomarkers and therapeutic targets, providing insights for IS diagnosis and therapy development.
缺血性中风（IS）是全球主要的死亡和残疾原因，与核苷酸代谢失衡有关。本研究旨在鉴定与IS相关的核苷酸代谢相关基因，并探索它们在疾病机制中的作用，以寻找新的诊断和治疗策略。
IS基因表达数据来源于GEO数据库。在R中进行差异表达分析和加权基因共表达网络分析（WGCNA），将结果与核苷酸代谢相关基因进行交叉。功能富集和连通性图谱（cMAP）分析确定关键基因和潜在治疗药物。使用LASSO回归、支持向量机递归特征消除（SVM-RFE）和随机森林算法确定核心免疫相关基因。通过CIBERSORT分析免疫细胞浸润水平和相关性。单细胞RNA测序（scRNA-seq）数据和分子对接评估基因表达、定位及基因-药物结合情况。实验验证核心基因表达。
鉴定出33个候选基因，主要参与免疫和炎症反应。 、 和 成为关键免疫相关基因，与免疫细胞浸润有关，具有较高诊断潜力。cMAP分析表明这些基因可作为药物靶点。scRNA-seq阐明了它们的表达和定位，分子对接证实了较强的药物结合。实验验证了它们在IS中的显著表达。
本研究强调了核苷酸代谢在IS中的作用，鉴定出 、 和 作为潜在生物标志物和治疗靶点，为IS诊断和治疗发展提供了见解。
