Establishment and validation of a bioinformatics ferroptosis gene diagnostic model for myocardial infarction and immunological analysis
- VernacularTitle:基于生物信息学建立与验证急性心肌梗死铁死亡基因诊断模型及免疫分析
- Author:
Yufang GONG
1
;
Haixia DENG
2
;
Yan LU
1
;
Wei ZHOU
1
Author Information
1. Department of Traditional Chinese Medicine, Guigang City People s Hospital, Guigang, 537000, Guangxi, P. R. China
2. Emergency Department, The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, 530022, P. R. China
- Publication Type:Journal Article
- Keywords:
Bioinformatics;
acute myocardial infarction;
ferroptosis;
artificial neural network;
immune infiltration
- From:
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery
2025;32(12):1754-1763
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish and validate the diagnostic model of ferroptosis genes for acute myocardial infarction (AMI) based on bioinformatics. Methods Five AMI gene expression data were obtained from Gene Expression Omnibus (GEO), namely GSE66360, GSE48060, GSE60993, GSE83500, GSE34198. Among them, GSE66360 was used as the training set to perform differential analysis, and intersection of differential genes and ferroptosis genes was taken to obtain differentially expressed ferroptosis genes in AMI. GO and KEGG enrichment analyses were performed using Metascape website. Subsequently, random forest (RF) algorithm was used to screen out key genes with high classification performance according to the Keeny coefficient score, and artificial neural network (ANN) diagnostic model of AMI ferroptosis feature gene was constructed by model group GSE83500. The area under the receiver operating characteristic curve (AUC) of 10-fold cross-validation was used to evaluate the performance and generalization ability of the model, and 3 external independent datasets were used to verify the diagnostic performance of this model. The single sample gene set enrichment analysis was used to explore the difference in immune cell infiltration between infarcted myocardium and normal myocardium after AMI. In addition, correlation analysis between immune cells and key genes was also conducted. Finally, potential drugs that would prevent and treat AMI by regulating ferroptosis were screened out from the Coremin Medical platform. Results A total of 16 differentially expressed ferroptosis genes were obtained in the training set, GO enrichment analysis showed that they mainly participated in biological functions such as cellular response to biological stimuli and chemical stress, and regulation of interleukin 17. KEGG enrichment analysis showed that these genes were significantly enriched in NOD-like receptor signaling pathway, programmed cell necrosis, Leishmaniasis and other pathways. Four genes with good classification performance were screened out using RF algorithm, namely EPAS1, SLC7A5, FTH1, and ZFP36. The results of 10-fold cross-validation showed that the minimum AUC value was 0.746, the maximum value was 0.906, and the average value was 0.805. The AUC of the ANN model was 0.859, and the AUC values of the three independent validation sets were 0.763 (GSE48060), 0.673 (GSE60993), 0.698 (GSE34198). Immune cell infiltration found that macrophages, mast cells and monocytes were significantly active after AMI. Correlation analysis found that there were positive correlations between 4 key genes and activated dendritic cells, eosinophils and γδT cells. A total of 20 potential western medicines were predicted which could prevent and treat AMI by regulating ferroptosis, and the predicted potential Chinese medicine was mainly heat-clearing and detoxifying and blood-activating and removing blood stasis drugs. Conclusion The identified AMI ferroptosis genes by bioinformatics method have certain diagnostic significance, which provides a reference for disease diagnosis and treatment.
