Wu Shuxing, Wang Ru, Cui Jian, Huo Hongjie, Yao Zhuhua
Department of Cardiology 1, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, 300121, China.
Department of Respiratory Medicine, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, 300121, China.
Biochem Genet. 2025 Aug 19. doi: 10.1007/s10528-025-11211-2.
This study aimed to identify diagnostic marker genes for myocardial infarction (MI) and analyzed the key genes pertaining to immune cell infiltration. The MI expression microarrays GSE48060 and GSE66360 were retrieved and downloaded from the GEO database. The merged expression data were subjected to Weighted Gene Co-expression Network Analysis (WGCNA). Subsequently, differentially expressed genes (DEGs) were analyzed in MI. Primary rat cardiomyocytes (NRVMs) were isolated for an oxygen-glucose deprivation/reoxygenation (OGD/R) model, in which the effect of ICAM1, NFIL3, TULP2, and ZFP36 on cell phenotype experiments was detected. Gene differential expression analysis identified 96 significant DEGs, and the intersection of these genes with the module genes obtained from WGCNA analysis yielded 81 candidate genes. LASSO regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms identified 7 candidate diagnostic genes. ICAM1, NFIL3, TULP2, and ZFP36 exhibited good diagnostic potential in both experimental and validation datasets, showing significant correlations with immune cells, including Neutrophils. ICAM1, NFIL3, TULP2, and ZFP36 were markedly up-regulated in OGD/R-treated NRVMs, while ICAM1 knockdown suppressed NRVM damage triggered by OGD/R. ICAM1, NFIL3, TULP2, and ZFP36 can serve as candidate diagnostic genes for MI, and ICAM1 silencing can ameliorate OGD/R-elicited myocardial cell damage.
本研究旨在识别心肌梗死（MI）的诊断标志物基因，并分析与免疫细胞浸润相关的关键基因。从基因表达综合数据库（GEO数据库）中检索并下载了MI表达微阵列GSE48060和GSE66360。对合并后的表达数据进行加权基因共表达网络分析（WGCNA）。随后，分析MI中的差异表达基因（DEG）。分离原代大鼠心肌细胞（NRVM）建立氧糖剥夺/复氧（OGD/R）模型，检测细胞间黏附分子1（ICAM1）、核因子IL3（NFIL3）、郁金香样蛋白2（TULP2）和锌指蛋白36（ZFP36）对细胞表型实验的影响。基因差异表达分析确定了96个显著的DEG，这些基因与WGCNA分析获得的模块基因的交集产生了81个候选基因。套索回归和支持向量机递归特征消除（SVM-RFE）算法确定了7个候选诊断基因。ICAM1、NFIL3、TULP2和ZFP36在实验数据集和验证数据集中均表现出良好的诊断潜力，与包括中性粒细胞在内的免疫细胞存在显著相关性。ICAM1、NFIL3、TULP2和ZFP36在OGD/R处理的NRVM中显著上调，而ICAM1基因敲低可抑制OGD/R引发的NRVM损伤。ICAM1、NFIL3、TULP2和ZFP36可作为MI的候选诊断基因，ICAM1沉默可改善OGD/R引起的心肌细胞损伤。
