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Immune Cell Infiltration Analysis Based on Bioinformatics Reveals Novel Biomarkers of Coronary Artery Disease
Tianwen He1,2, Muheremu Muhetaer1,2, Jiahe Wu1,2
1Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.
Insights
Researchers identified CHFR, CEL, and CCDC28A as novel immune-related biomarkers for coronary artery disease (CAD). These findings offer potential for early noninvasive diagnosis and immunotherapy of this complex immune condition.
Area of Science:
- Immunology
- Genomics
- Biomarker Discovery
Background:
- Coronary artery disease (CAD) is recognized as a multifactorial immune disease.
- Specific immune mechanisms underlying CAD require further investigation.
- Identifying novel immune-related markers is crucial for understanding and managing CAD.
Purpose of the Study:
- To identify novel immune-related biomarkers for coronary artery disease (CAD).
- To explore the role of immune cell infiltration in CAD pathogenesis.
- To validate potential diagnostic and therapeutic targets for CAD.
Main Methods:
- Utilized three CAD-related gene expression datasets (GSE12288, GSE98583, GSE113079).
- Performed Gene Ontology, KEGG pathway, and weighted gene co-expression network analyses on differentially expressed genes (DEGs).
- Employed CIBERSORT for immune cell infiltration analysis and LASSO regression for characteristic gene identification and validation in clinical samples.
Main Results:
- Identified 204 upregulated and 339 downregulated DEGs, enriched in pathways like 'Apoptosis' and 'Th17 cell differentiation'.
- Five characteristic genes (LMAN1L, DOK4, CHFR, CEL, CCDC28A) were identified using LASSO regression.
- Observed lower proportions of activated CD8 T cells and CD56 DIM natural killer cells in CAD patients; CHFR, CEL, and CCDC28A showed differential expression in patient blood samples.
Conclusions:
- CHFR, CEL, and CCDC28A are identified as potential biomarkers associated with immune infiltration in CAD.
- These biomarkers may serve as targets for early noninvasive diagnosis of CAD.
- The findings contribute to developing potential immunotherapy strategies for coronary artery disease.
Background:
Coronary artery disease (CAD) is a multifactorial immune disease, but research into the specific immune mechanism is still needed. The present study aimed to identify novel immune-related markers of CAD.
Methods:
Three CAD-related datasets (GSE12288, GSE98583, GSE113079) were downloaded from the Gene Expression Integrated Database. Gene ontology annotation, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and weighted gene co-expression network analysis were performed on the common significantly differentially expressed genes (DEGs) of these three data sets, and the most relevant module genes for CAD obtained. The immune cell infiltration of module genes was evaluated with the CIBERSORT algorithm, and characteristic genes accompanied by their diagnostic effectiveness were screened by the machine-learning algorithm least absolute shrinkage and selection operator (LASSO) regression analysis. The expression levels of characteristic genes were evaluated in the peripheral blood mononuclear cells of CAD patients and healthy controls for verification.
Results:
A total of 204 upregulated and 339 downregulated DEGs were identified, which were mainly enriched in the following pathways: "Apoptosis", "Th17 cell differentiation", "Th1 and Th2 cell differentiation", "Glycerolipid metabolism", and "Fat digestion and absorption". Five characteristic genes, LMAN1L, DOK4, CHFR, CEL and CCDC28A, were identified by LASSO analysis, and the results of the immune cell infiltration analysis indicated that the proportion of immune infiltrating cells (activated CD8 T cells and CD56 DIM natural killer cells) in the CAD group was lower than that in the control group. The expressions of CHFR, CEL and CCDC28A in the peripheral blood of the healthy controls and CAD patients were significantly different.
Conclusion:
We identified CHFR, CEL and CCDC28A as potential biomarkers related to immune infiltration in CAD based on public data sets and clinical samples. This finding will contribute to providing a potential target for early noninvasive diagnosis and immunotherapy of CAD.
