Background: Acute myocardial infarction (AMI) is a major cause of human health risk. Necroptosis is a newly and recently reported mode of cell death, whose role in AMI has not been fully elucidated. This study aimed to search for necroptosis biomarkers associated with the occurrence of AMI and to explore their possible molecular mechanisms through bioinformatics analysis.

Methods: The dataset GSE48060 was used to perform weighted gene co-expression network analysis (WGCNA) and differential analysis. Key modules, differential genes, and necroptosis-related genes (NRGs) were intersected to obtain candidate biomarkers. Groups were classified and differentially analyzed according to the expression of the key biomarker. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, gene set enrichment analysis (GSEA), and construction of protein-protein interaction (PPI) networks are performed on differentially expressed genes (DEGs). Finally, CIBERSORT was used to assess immune cell infiltration in AMI and the correlation of key biomarkers with immune cells. Immune cell infiltration analysis revealed the correlation between FASLG and multiple screened immune cells.

Results: WGCNA determined that the MEsaddlebrown module was the most significantly associated with AMI. Intersecting it with DEGs as well as NRGs, we obtained two key genes, FASLG and IFNG. But only FASLG showed statistically significant differences between the AMI group and the normal control group. Further analysis suggested that the down-regulation of FASLG may exert its function through the regulation of the central genes CD247 and YES1. Furthermore, FASLG was positively correlated with T-cell CD4 memory activation and T-cell gamma delta, and negatively correlated with macrophage M0.

Conclusion: In conclusion, FASLG and its regulatory genes CD247 and YES1 might be involved in the development of AMI by regulating immune cell infiltration. FASLG might be a potential biomarker for AMI and provides a new direction for the diagnosis of AMI.

Keywords: Acute myocardial infarction; Bioinformatics; FASLG; Immune infiltration; Necroptosis.

Copyright 2024, Jia et al.

背景： 急性心肌梗死（AMI）是人类健康风险的主要原因之一。坏死性凋亡是一种新近报道的细胞死亡方式，其在AMI中的作用尚未完全阐明。本研究旨在寻找与AMI发生相关的坏死性凋亡生物标志物，并通过生物信息学分析探讨它们可能的分子机制。

方法： 使用数据集GSE48060进行加权基因共表达网络分析（WGCNA）和差异分析。关键模块、差异基因以及坏死性凋亡相关基因（NRGs）相交以获取候选生物标志物。根据关键生物标志物的表达对组进行分类并进行差异分析。在差异表达基因（DEGs）上执行基因本体论（GO）、京都基因和基因组百科全书（KEGG）富集分析、基因集合富集分析（GSEA）以及构建蛋白质-蛋白质相互作用（PPI）网络。最后，使用CIBERSORT评估AMI中的免疫细胞浸润，并确定关键生物标志物与免疫细胞的相关性。免疫细胞浸润分析揭示了FASLG和多个筛选出的免疫细胞之间的相关性。

结果： WGCNA确定MEsaddlebrown模块最显著地与AMI相关联。将该模块与DEGs以及NRGs相交后，我们获得了两个关键基因：FASLG和IFNG。但只有FASLG在AMI组和正常对照组之间表现出统计学上的显著差异。进一步分析表明，FASLG的下调可能通过调控中心基因CD247和YES1来发挥作用。此外，FASLG与T细胞CD4记忆激活以及T细胞γδ呈正相关，并与巨噬细胞M0呈负相关。

结论： 总之，FASLG及其调控基因CD247和YES1可能通过调节免疫细胞浸润参与AMI的发展。FASLG可能是AMI的一个潜在生物标志物，并为AMI的诊断提供了新的方向。

关键词： 急性心肌梗死；生物信息学；FASLG；免疫浸润；坏死性凋亡。