Integrated Multichip Analysis and WGCNA Identify Potential Diagnostic Markers in the Pathogenesis of ST-Elevation
Yingliang Liang1, Wandang Wang1, Qiufang Huang1
1Department of Clinical Laboratory, Xiaolan People's Hospital of Zhongshan, Zhongshan, Guangdong, China.
Insights
New diagnostic markers, ALOX5AP and BST1, for ST-elevation myocardial infarction (STEMI) were identified. Immune cell infiltration is crucial in STEMI development, with specific cell types correlating to these markers.
Area of Science:
- Cardiovascular Biology
- Immunology
- Genomics
Background:
- ST-elevation myocardial infarction (STEMI) is a critical condition caused by epicardial vascular occlusion.
- Current diagnostic markers for STEMI are limited, necessitating the identification of novel biomarkers.
Purpose of the Study:
- To identify novel diagnostic biomarkers for STEMI using gene expression data.
- To investigate the role of immune cell infiltration in the pathogenesis of STEMI.
Main Methods:
- Differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) were performed on STEMI microarray data.
- Pathway enrichment analyses (GO, KEGG) and protein-protein interaction network construction were utilized.
- Machine learning algorithms (LASSO, SVM-RFE) identified diagnostic biomarkers, and CIBERSORT assessed immune cell infiltration.
Main Results:
- 710 differentially expressed genes (DEGs) and 92 intersection genes were identified, enriched in 30 Gene Ontology (GO) terms and 2 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.
- ALOX5AP and BST1 were confirmed as highly accurate diagnostic markers for STEMI (AUC=1.00).
- STEMI is associated with altered infiltration of CD8+T cells, regulatory T cells, NK cells, M0 macrophages, mast cells, and neutrophils. ALOX5AP and BST1 expression correlated with these immune cell populations.
Conclusions:
- ALOX5AP and BST1 show significant potential as diagnostic markers for ST-elevation myocardial infarction.
- Immune cell infiltration is a key factor in STEMI development and progression, with specific correlations to identified biomarkers.
Background:
ST-elevation myocardial infarction (STEMI) is a myocardial infarction (MI) with ST-segment exaltation of electrocardiogram (ECG) caused by vascular occlusion of the epicardium. However, the diagnostic markers of STEMI remain little.
Methods:
STEMI raw microarray data are acquired from the Gene Expression Omnibus (GEO) database. Based on GSE60993 and GSE61144, differentially expressed genes (DEGs) are verified via R software, and key modules associated with pathological state of STEMI are verified by weighted correlation network analysis (WGCNA). Take the intersection gene of key module and DEGs to perform the pathway enrichment analyses by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Construct the protein-protein interaction (PPI) network by Cytoscape. Then, select and identify the diagnostic biomarkers of STEMI by least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms. Finally, assess the infiltration of immune cells of STEMI by CIBERSORT and analyze the correlation between diagnostic markers and infiltrating immune cells.
Results:
We get 710 DEGs in the STEMI group and 376 genes associated with STEMI in blue module. 92 intersection genes were concentrated in 30 GO terms and 2 KEGG pathways. 28 hub genes involved in the development of STEMI. Moreover, upregulated ALOX5AP (AUC = 1.00) and BST1 (AUC = 1.00) are confirmed as diagnostic markers of STEMI. CD8+T cells, regulatory T (Treg) cells, resting natural killer (NK) cells, M0 macrophages, resting mast cells, and neutrophils are related to the procession of STEMI. Moreover, ALOX5AP and BST1 are positively related to resting NK cells, M0 macrophages, and neutrophils, while ALOX5AP and BST1 are negatively related to CD8+ T cells, Treg cells, and resting mast cells.
Conclusion:
ALOX5AP and BST1 may be the diagnostic markers of STEMI. Immune cell infiltration plays a key role in the development of STEMI.
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