Identification of a novel immune infiltration-related gene signature, MCEMP1, for coronary artery disease
Wei Ye1,2,3,4, Bo Shen2,3, Qizhu Tang2,3
1Department of Neonatology, Renmin Hospital of Wuhan University, Wuhan, China.
Insights
Mast cell-expressed membrane protein 1 (MCEMP1) is identified as a key gene in coronary artery disease (CAD). MCEMP1 influences immune cell infiltration and endothelial cell function, suggesting its role in CAD development.
Area of Science:
- Genomics and Bioinformatics
- Immunology
- Cardiovascular Research
Background:
- Coronary artery disease (CAD) pathogenesis involves complex genetic and immune factors.
- Identifying novel gene signatures and understanding immune cell roles are crucial for CAD research.
- Mast cell-expressed membrane protein 1 (MCEMP1) function in endothelial cells under oxidative stress is largely unexplored.
Purpose of the Study:
- To identify a novel gene signature for coronary artery disease (CAD).
- To investigate the role of immune cell infiltration in CAD pathogenesis.
- To assess the functional role of MCEMP1 in human umbilical vein endothelial cells (HUVECs) exposed to oxidized low-density lipoprotein (ox-LDL).
Main Methods:
- Differential gene expression analysis using GEO datasets (GSE24519, GSE61145) and R 'limma' package.
- Gene Ontology (GO) and KEGG pathway analyses for functional enrichment.
- Hub gene identification via SVM-RFE and LASSO; validation in GSE113079 dataset.
- Immune cell infiltration quantification using CIBERSORT.
- Western blot, qRT-PCR, CCK8 assay, Muse® Cell Analyzer, and ELISA for functional validation of MCEMP1.
Main Results:
- 73 differentially expressed genes (DEGs) identified, associated with platelet aggregation, immune response, and atherosclerosis.
- Seven hub genes identified, with upregulated DIRC2 and MCEMP1 validated in CAD datasets and ox-LDL-treated HUVECs.
- MCEMP1 knockdown in HUVECs promoted proliferation, inhibited apoptosis, and reduced inflammatory cytokine (IL-1β, IL-6, TNF-α) expression.
Conclusions:
- MCEMP1 is identified as a significant hub gene in coronary artery disease.
- MCEMP1 expression is linked to immune cell infiltration and inflammatory responses in CAD.
- MCEMP1 plays a crucial role in the pathophysiology of coronary artery disease.
Background:
This study aims to identify a novel gene signature for coronary artery disease (CAD), explore the role of immune cell infiltration in CAD pathogenesis, and assess the cell function of mast cell-expressed membrane protein 1 (MCEMP1) in human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL).
Methods:
To identify differentially expressed genes (DEGs) of CAD, datasets GSE24519 and GSE61145 were downloaded from the Gene Expression Omnibus (GEO) database using the R "limma" package with p < 0.05 and |log2 FC| > 1. Gene ontology (GO) and pathway analyses were conducted to determine the biological functions of DEGs. Hub genes were identified using support vector machine-recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO). The expression levels of these hub genes in CAD were validated using the GSE113079 dataset. CIBERSORT program was used to quantify the proportion of immune cell infiltration. Western blot assay and qRT-PCR were used to detect the expression of hub genes in ox-LDL-treated HUVECs to validate the bioinformatics results. Knockdown interference sequences for MCEMP1 were synthesized, and cell proliferation and apoptosis were examined using a CCK8 kit and Muse® Cell Analyzer, respectively. The concentrations of IL-1β, IL-6, and TNF-α were measured with respective enzyme-linked immunosorbent assay (ELISA) kits.
Results:
A total of 73 DEGs (four down-regulated genes and 69 up-regulated genes) were identified in the metadata (GSE24519 and GSE61145) cohort. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results indicated that these DEGs might be associated with the regulation of platelet aggregation, defense response or response to bacterium, NF-kappa B signaling pathway, and lipid and atherosclerosis. Using SVM-RFE and LASSO, seven hub genes were obtained from the metadata. The upregulated expression of DIRC2 and MCEMP1 in CAD was confirmed in the GSE113079 dataset and in ox-LDL-treated HUVECs. The associations between the two hub genes (DIRC2 and MCEMP1) and the 22 types of immune cell infiltrates in CAD were found. MCEMP1 knockdown accelerated cell proliferation and suppressed cell apoptosis for ox-LDL-treated HUVECs. Additionally, MCEMP1 knockdown appeared to decrease the expression of inflammatory factors IL-1β, IL-6, and TNF-α.
Conclusions:
The results of this study indicate that MCEMP1 may play an important role in CAD pathophysiology.
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