Tang Qiu-Rong, Feng Yang, Zhao Yao, Bian Yun-Fei
Department of Cardiology,Second Hospital of Shanxi Medical University,Taiyuan 030000,China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2025 Jun 30;47(3):354-365. doi: 10.3881/j.issn.1000-503X.16057.
Objective To identify disulfidptosis-related gene(DRG)in acute myocardial infarction(AMI)by bioinformatics,analyze the molecular pattern of DRGs in AMI,and construct a DRGs-related prediction model.Methods AMI-related datasets were downloaded from the Gene Expression Omnibus database,and DRGs with differential expression were screened in AMI.CIBERSORT method was used to analyze the immune infiltration.Based on the differentially expressed DRGs,the AMI patients were classified into distinct subtypes via consensus clustering,followed by immune infiltration analysis,differential expression analysis,gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis,and gene set variation analysis.Weighted gene co-expression network analysis(WGCNA)was then performed to construct subtype-associated modules and identify hub genes.Finally,least absolute shrinkage and selection operator,random forest,and support vector machine-recursive feature elimination were used to screen feature genes to construct a DRGs-related prediction model.The model's diagnostic efficacy was evaluated by nomogram and receiver operating characteristic(ROC)curve analysis,followed by external validation.Results Nine differentially expressed DRGs were identified between AMI patients and controls.Based on the expression levels of these nine DRGs,AMI patients were divided into two DRGs subtypes,C1 and C2.Increased infiltration of monocytes,M0 macrophages,and neutrophils was observed in AMI patients and C1 subtype(all <0.05),indicating a close correlation between DRGs and immune cells.There were 257 differentially expressed genes between the C1 and C2 subtypes,which were related to biological processes such as myeloid leukocyte activation and positive regulation of cytokines.Fcγ receptor-mediated phagocytosis and NOD-like receptor signaling pathway activity were enhanced in C1 subtype.WGCNA analysis suggested that the brown module exhibited the strongest correlation with DRG subtypes(=0.67),from which 23 differentially expressed genes were identified.The feature genes screened by three machine learning methods were interpolated to obtain a DRGs-related prediction model consisting of three genes(AQP9,F5 and PYGL).Nomogram and ROC curves(AUC=0.891,AUC=0.840)showed good diagnostic efficacy.Conclusions DRGs were closely related to the occurrence and progression of AMI.The DRGs-related prediction model consisting of AQP9,F5 and PYGL may provide targets for the diagnosis and personalized treatment of AMI.
目的 通过生物信息学方法鉴定急性心肌梗死(AMI)中与二硫化物依赖性细胞程序性坏死相关的基因(DRG),分析DRG在AMI中的分子模式,并构建与DRG相关的预测模型。方法 从基因表达综合数据库下载与AMI相关的数据集,筛选出AMI中差异表达的DRG。采用CIBERSORT方法分析免疫浸润情况。基于差异表达的DRG,通过一致性聚类将AMI患者分为不同亚型,随后进行免疫浸润分析、差异表达分析、基因本体论和京都基因与基因组百科全书富集分析以及基因集变异分析。然后进行加权基因共表达网络分析(WGCNA)以构建与亚型相关的模块并鉴定枢纽基因。最后,使用最小绝对收缩和选择算子、随机森林以及支持向量机递归特征消除法筛选特征基因以构建与DRG相关的预测模型。通过列线图和受试者工作特征(ROC)曲线分析评估该模型的诊断效能,随后进行外部验证。结果 在AMI患者和对照组之间鉴定出9个差异表达的DRG。基于这9个DRG的表达水平,将AMI患者分为两个DRG亚型,C1和C2。在AMI患者和C1亚型中观察到单核细胞、M0巨噬细胞和中性粒细胞浸润增加(均<0.05),表明DRG与免疫细胞密切相关。C1和C2亚型之间有257个差异表达基因,这些基因与髓系白细胞活化和细胞因子的正调控等生物学过程相关。C1亚型中Fcγ受体介导的吞噬作用和NOD样受体信号通路活性增强。WGCNA分析表明棕色模块与DRG亚型的相关性最强(=0.67),从中鉴定出23个差异表达基因。通过三种机器学习方法筛选出的特征基因进行插值,得到一个由三个基因(AQP9、F5和PYGL)组成的与DRG相关的预测模型。列线图和ROC曲线(AUC = 0.891,AUC = 0.840)显示出良好的诊断效能。结论 DRG与AMI的发生和发展密切相关。由AQP9、F5和PYGL组成的与DRG相关的预测模型可能为AMI的诊断和个性化治疗提供靶点。