Hereditas (Dec 2021)
Identification of crucial genes involved in pathogenesis of regional weakening of the aortic wall
Abstract
Abstract Background The diameter of the abdominal aortic aneurysm (AAA) is the most commonly used parameter for the prediction of occurrence of AAA rupture. However, the most vulnerable region of the aortic wall may be different from the most dilated region of AAA under pressure. The present study is the first to use weighted gene coexpression network analysis (WGCNA) to detect the coexpressed genes that result in regional weakening of the aortic wall. Methods The GSE165470 raw microarray dataset was used in the present study. Differentially expressed genes (DEGs) were filtered using the “limma” R package. DEGs were assessed by Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. WGCNA was used to construct the coexpression networks in the samples with regional weakening of the AAA wall and in the control group to detect the gene modules. The hub genes were defined in the significant functional modules, and a hub differentially expressed gene (hDEG) coexpression network was constructed with the highest confidence based on protein–protein interactions (PPIs). Molecular compound detection (MCODE) was used to identify crucial genes in the hDEG coexpression network. Crucial genes in the hDEG coexpression network were validated using the GSE7084 and GSE57691 microarray gene expression datasets. Result A total of 350 DEGs were identified, including 62 upregulated and 288 downregulated DEGs. The pathways were involved in immune responses, vascular smooth muscle contraction and cell–matrix adhesion of DEGs in the samples with regional weakening in AAA. Antiquewhite3 was the most significant module and was used to identify downregulated hDEGs based on the result of the most significant modules negatively related to the trait of weakened aneurysm walls. Seven crucial genes were identified and validated: ACTG2, CALD1, LMOD1, MYH11, MYL9, MYLK, and TPM2. These crucial genes were associated with the mechanisms of AAA progression. Conclusion We identified crucial genes that may play a significant role in weakening of the AAA wall and may be potential targets for medical therapies and diagnostic biomarkers. Further studies are required to more comprehensively elucidate the functions of crucial genes in the pathogenesis of regional weakening in AAA.
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