Identification of Macrophage-related Gene Signature Associated with Unstable Atherosclerotic Plaques through Integrative Multi- omics Analysis

Abstract

Background: Macrophages play a crucial role in the occurrence and development of atherosclerosis. The purpose of this study is to identify critical candidate genes associated with unstable atherosclerotic plaques in macrophages Methods: The single-cell sequencing dataset GSE159677 and microarray datasets GSE43292 and GSE100927 were downloaded from the Gene Expression Omnibus database. The intersection of differential analysis results from single-cell transcriptome sequencing data, microarray data, immune infiltration analysis, and WGCNA analysis results yielded macrophage-related genes. Least absolute shrinkage, and selection operator (LASSO) was utilized for screening characteristic genes among atherosclerotic plaque progression- and macrophage-related genes. ROC curves were produced to evaluate the diagnostic performance. Finally, pseudo-time analysis was used to obtain the expression patterns of key genes along the cell differentiation trajectory. Results: Based on multiple omics analyses, we obtained 59 genes related to macrophages. Then, by using the LASSO algorithm to select features, we ultimately obtained five key genes. Using these five genes, we constructed a nomogram diagnostic model that demonstrated high diagnostic performance in both the training (AUC=0.882) and testing (AUC=0.985) datasets. Pseudo-time analysis shows that STAB1 is exclusively expressed in resident macrophages, while IL1RN expression gradually increases over time. DAB2 is highly expressed in both resident and foamy macrophages. NLRP3 expression is found in some cells of resident and inflammatory macrophages, but not at all in foam cells. HMOX1 expression varies little across different cell types. Conclusion: Our study has identified a gene signature consisting of STAB1, NLRP3, IL1RN, HMOX1, and DAB2 through integrative multi-omics analysis, which may play a crucial role in the development and progression of atherosclerosis.