Identification of ABCB1 in the ATP-Binding Cassette Transporter Protein Family as a Diagnostic Biomarker for Ath-erosclerosis
Objective:The ATP-binding cassette(ABC)transporter protein gene family influences the development of ath-erosclerotic disease,and the genes in the ABC transporter protein gene family that are associated with the diagnosis of athero-sclerosis(AS)were investigated through Gene Expression Omnibus(GEO)data mining to explore potential AS markers.Methods:A total of 4 alternative datasets(GSE43292,GSE40231,GSE100927,and GSE21545)were included,containing a total of 267 AS patients and 204 controls for analysis.To identify ABC family genes,statistical analyses were used in this study,such as ROC analysis,t test and Mann-Whitney U test.Protein-protein interaction(PPI)network creation and path-way analysis were performed using the Searching the Database of Interacting Genes/Proteins(STRING)database and the Da-tabase for Annotation,Visualization and Integrated Discovery(DAVID).And weighted gene co-expression network analysis(WGCNA)and gene set enrichment analysis(GSEA)were used for functional analysis.Finally,the core genes were ana-lyzed by immune infiltration.Results:After several rounds of screening and confirmation,only the ABCB1(P＜0.05,AUC＞0.85)gene was retained among 48 genes.20 genes directly interacting with ABCB1 were obtained from the STRING da-tabase,and the PPI network was constructed using Cytoscape 3.9.1 software.These 21 genes were analyzed for GO and KEGG enrichment,and were found to function mainly in various metabolic pathways.GSEA analysis showed that ABCB1 was enriched in a total of 112 pathways,of which 40 were associated with high expression of ABCB1 and 72 with low expression of ABCB1.WGCNA analysis identified a total of 14 gene modules(β=3)associated with ABCB1 expression in AS,of which the turquoise module was the most strongly correlated with ABCB1(Cor=0.98,P＜0.001),which contained a total of 4 517 genes.GO and KEGG enrichment analysis of the genes in this module showed that ABCB1 was associated in cell adhesion,angiogenesis,focal adhesion,ECM receptor interaction and PI3K-Akt signaling pathway.The results of immune infiltration analysis showed a signif-icant increase in activated mast cells and MO,M1,and M2 macrophages and a significant decrease in T lymphocytes,inactivated NK cells,and monocytes in the AS group.Conclusion:This study found that ABCB1 has good diagnostic value and is signifi-cantly expressed in AS patients.These findings may provide direction for future management and treatment of AS.
AtherosclerosisABCB1Gene set enrichment analysisWeighted co-expression network analysisIm-mune infiltration analysis
万方数据
维普
