General Practice, Guangzhou Red Cross Hospital, Guangzhou, China.
Neurology, Guangzhou Red Cross Hospital, Guangzhou, China.
PeerJ. 2024 Feb 26;12:e17044. doi: 10.7717/peerj.17044. eCollection 2024.
Acute myocardial infarction (AMI) can occur suddenly, which may induce deadly outcomes, and the population suffering from AMI presents a younger trend. Necroptosis, the new cell necrosis type, is associated with the pathogenic mechanisms of diverse cardiovascular diseases (CVDs). Its diagnostic value and molecular mechanisms in AMI are still unclear. Objective: This study focused on determining key necroptosis-related genes as well as immune infiltration in AMI.
We first examined the GSE66360 dataset for identifying necroptosis-related differentially expressed genes (NRDEGs). Thereafter, GO and functional annotation were performed, then a PPI network was built. In addition, "CIBERSORT" in R was applied in comparing different immune infiltration degrees in AMI compared with control groups. The receiver operating characteristic (ROC) curve was plotted to evaluate whether hub NRDEGs could be used in AMI diagnosis. Associations of immune cells with candidate NRDEGs biomarkers were examined by Spearman analysis. Finally, hub NRDEGs were validated by cell qPCR assays and another two datasets.
A total of 15 NRDEGs were identified and multiple enrichment terms associated with necroptosis were discovered through GO and KEGG analysis. Upon module analysis, 10 hub NRDEGs were filtered out, and the top six hub NRDEGs were identified after ROC analysis. These top six NRDEGs might have a certain effect on modulating immune infiltrating cells, especially for mast cells activated, NK cells activated and neutrophils. Finally, two AMI datasets and qPCR assay came to identical findings.
Our results offer the reliable molecular biomarkers and new perspectives for necroptosis in AMI, which lay a certain foundation for developing novel anti-AMI therapeutic targets.
急性心肌梗死（AMI）可突然发生，这可能导致致命的后果，且患有 AMI 的人群呈现年轻化趋势。坏死性凋亡是一种新的细胞坏死类型，与多种心血管疾病（CVDs）的发病机制有关。其在 AMI 中的诊断价值和分子机制尚不清楚。目的：本研究旨在确定关键的坏死性凋亡相关基因和 AMI 中的免疫浸润。
我们首先检查了 GSE66360 数据集，以鉴定与坏死性凋亡相关的差异表达基因（NRDEGs）。然后进行了 GO 和功能注释，然后构建了 PPI 网络。此外，在 R 中应用了“CIBERSORT”来比较 AMI 与对照组之间不同的免疫浸润程度。绘制接收者操作特征（ROC）曲线，以评估核心 NRDEGs 是否可用于 AMI 诊断。通过 Spearman 分析检查候选 NRDEGs 生物标志物与免疫细胞的相关性。最后，通过细胞 qPCR 检测和另外两个数据集验证了核心 NRDEGs。
共鉴定出 15 个 NRDEGs，并通过 GO 和 KEGG 分析发现了与坏死性凋亡相关的多个富集项。通过模块分析，筛选出 10 个核心 NRDEGs，经过 ROC 分析后确定了前 6 个核心 NRDEGs。这前 6 个 NRDEGs 可能对调节免疫浸润细胞有一定的影响，尤其是对激活的肥大细胞、激活的自然杀伤细胞和中性粒细胞。最后，两个 AMI 数据集和 qPCR 检测得出了相同的结果。
我们的研究结果为 AMI 中的坏死性凋亡提供了可靠的分子生物标志物和新视角，为开发新型抗 AMI 治疗靶点奠定了一定的基础。
