The bioinformatics analysis of sex-related gene expression differences in abdominal aortic aneurysm
Objective Investigating sex-related gene expression differences in abdominal aortic an-eurysm(AAA)through bioinformatics methods and identifying key genes.Methods Datasets GSE7084,GSE197748,and GSE57691 were downloaded from the Gene Expression Omnibus(GEO)database.Differ-ential analysis was performed on the samples in the GSE7084 and GSE197748 datasets based on sex.A protein-protein interaction(PPI)network was constructed for male-specific differentially expressed genes(msDEGs)and common differentially expressed genes(cDEGs).Metascape was used to conduct Gene On-tology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment anal-ysis for intersecting genes.Immune infiltration was assessed using the CIBERSORT algorithm and mMCP-counter.Key genes from the cDEGs were selected using the least absolute shrinkage and selection operator(LASSO)and random forest(RF)algorithms,and the diagnostic performance of the key genes for AAA was evaluated using receiver operating characteristic(ROC)curves in the GSE7084 and GSE57691 data-sets.Finally,drugs interacting with the key genes were identified using the DGIdb database.Results In this study,a total of 112 msDEGs and 42 cDEGs were obtained.Enrichment analysis indicated that ms-DEGs were primarily enriched in inflammation-related pathways and immune-related pathways associated with myeloid cells,mainly regulated by the transcription factors RELA and NFKB1.In contrast,cDEGs were primarily enriched in pathways related to smooth muscle cell function,regulated by the transcription factors KLF5 and ETS1.The monocyte immune infiltration score in the male AAA group was higher than in the female AAA group(0.138±0.031 vs.0.018±0.013,t=-4.581,P＜0.05).By screening cDEGs,we identified two key genes:interleukin-2 receptor gamma chain(IL2RG)and leucine-rich repeat-containing G-protein coupled receptor 6(LGR6).In the GSE7084 dataset,the area under the curve(AUC)for diagnosing AAA with these two genes was 1 and 1,respectively;in the GSE7084 dataset,the AUCs were 0.92 and 0.91,respectively.Through the DGIdb database,13 potential targeting drugs were i-dentified.Conclusion Nuclear factor-KB(NF-κB)-mediated inflammatory response and myeloid cell-re-lated immune response are more pronounced in male AAA.
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