Identification of Hub Immune-Related Genes and Immune Infiltration in Type A Aortic Dissection by Bioinformatics Analysis

Abstract

Abstract Background: Type A Aortic Dissection (TAAD), a devastating cardiovascular emergency with high incidence, is associated with immune inflammation. Intervention targets and regulatory mechanism of TAAD remain unclear and necessitate further research. Three datasets (GSE153434, GSE52093, GSE190635) of TAAD were downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were explored, and immune-related genes, WGCNA and DEGs (IRWDEGs) were overlapped. Four hub genes were screened from 132 IRWDEGs by Protein-Protein Interaction (PPI) Network and least absolute shrinkage selection operator (LASSO) constructed by GSE52093 and validated by GSE190635 and GSE153434 merged datasets . The hub genes were further validated by the GSE52093 dataset and in TAAD tissues by using polymerase chain reaction(PCR) . Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene set enrichment analysis (GSEA) were constructed to explore potential related signaling pathways. Immune cell infiltration in TAAD was analyzed by ssGSEA, and their association with the four hub genes were explored. Results: A total of 132 IRWDEGs were overlapped, twelve key modules were screened, and finally 4 hub genes including CCL2, CXCL8, ENG, and TEK were identified. The expression of CCL2, CXCL8 and ENG was predicted to increase, whereas TEK was predicted to decrease. These results were verified in another independent dataset and human TAAD tissues. The hub genes were related to immune infiltration, indicated by type 17 T helper cell, activated dendritic cell, and active B cell. Conclusion: The effect of CCL2, CXCL8, ENG and TEK in immune infiltration were identified.