【摘要】 目的：识别与动脉粥样硬化（Atherosclerosis,AS）细胞焦亡（Pyroptosis）相关的基因，为研究动脉粥样硬化细胞焦亡的发病机制提供参考。方法：通过基因表达综合数据库（Gene Expression Omnibus,GEO）和基因卡片数据库（Gene Cards）分别获取AS相关GSE100927数据集和细胞焦亡相关基因（Pyroptosis-Related Genes,PRGs）数据集。利用R软件中的Limma包筛选出AS组与正常组之间的差异基因，并通过韦恩图映射差异基因与PRGs之间的共享基因。对共享基因进行基因本体论（Gene Ontology,GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes,KEGG）分析，并构建蛋白质-蛋白质相互作用（Protein-Protein Interaction,PPI）网络以筛选出与AS和细胞焦亡相关的关键基因。在训练集GSE100927和验证集GSE43292中验证关键基因在AS组与正常组中的差异表达，并通过ROC分析评估关键基因在AS中的诊断效能。结果：筛选出75个AS与细胞焦亡的共享基因（Pyroptosis-Atherosclerosis overlapping Genes,PRASGs）。KEGG富集分析主要富集于NOD样受体信号通路、脂质和动脉粥样硬化、胞质DNA感应通路、NF-kappa B信号通路、Toll样受体信号通路、坏死性凋亡、细胞因子-细胞因子受体相互作用、糖尿病并发症中的AGE-RAGE信号通路等。通过PPI网络和最小绝对收缩和选择算法（Least Absolute Shrinkage and Selection Operator,LASSO）分析确定了6个动脉粥样硬化细胞焦亡密切相关的关键基因：IFIH1、PPARG、EGFR、APOE、NLRC4和MMP9。在训练集GSE100927和验证集GSE43292中6个关键基因在AS组与正常组中表现出显著差异，最终ROC曲线显示6个关键基因具有很高的诊断价值。结论：筛选所得IFIH1、PPARG、EGFR、APOE、NLRC4和MMP9关键基因可作为动脉粥样硬化细胞焦亡相关的分子标志物。更多还原

【Abstract】 Objective: To identify genes associated with pyroptosis in atherosclerosis(AS) using bioinformatics analysis and to provide insights into the underlying mechanisms. Methods: The AS-related dataset GSE100927 was obtained from the Gene Expression Omnibus(GEO) database, and pyroptosis-related genes(PRGs) were retrieved from the Gene Cards database. Differentially expressed genes(DEGs) between AS and normal samples were identified using the limma package in R. Overlapping genes between DEGs and PRGs were identified using a Venn diagram.Functional enrichment analyses, including Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG), were performed. A protein-protein interaction(PPI) network was constructed to identify key genes. Least absolute shrinkage and selection operator(LASSO) regression was applied to further screen candidate genes. The expression of key genes was validated in the training set GSE100927 and the validation set GSE43292. Receiver operating characteristic(ROC) analysis was performed to evaluate their diagnostic performance. Results: A total of 75 overlapping genes(PRASGs) were identified. KEGG enrichment analysis revealed that these genes were mainly involved in the NOD-like receptor signaling pathway, lipid and atherosclerosis pathway, cytosolic DNA-sensing pathway,NF-κB signaling pathway, Toll-like receptor signaling pathway, necroptosis, cytokine-cytokine receptor interaction, and AGE-RAGE signaling pathway in diabetic complications. Six key genes(IFIH1, PPARG, EGFR, APOE, NLRC4 and MMP9) were identified through PPI network analysis and LASSO regression. These genes showed significant differential expression between AS and normal samples in both the training and validation datasets. ROC analysis demonstrated that the six genes exhibited high diagnostic value for AS. Conclusion: IFIH1, PPARG, EGFR, APOE, NLRC4 and MMP9 may serve as potential molecular biomarkers associated with pyroptosis in atherosclerosis.更多还原