Exploratory Study of Differentially Expressed Genes of Peripheral Blood Monocytes in Patients with Carotid Atherosclerosis

Juhai Chen; Fengyan Xu; Xiangang Mo; Yiju Cheng; Lan Wang; Hui Yang; Jiajing Li; Shiyue Zhang; Shuping Zhang; Nannan Li; Yang Cao

doi:10.2174/1386207326666230822122045

Exploratory Study of Differentially Expressed Genes of Peripheral Blood Monocytes in Patients with Carotid Atherosclerosis

Comb Chem High Throughput Screen. 2023 Aug 22. doi: 10.2174/1386207326666230822122045. Online ahead of print.

Authors

Juhai Chen^{1

2}, Fengyan Xu³, Xiangang Mo³, Yiju Cheng⁴, Lan Wang³, Hui Yang³, Jiajing Li³, Shiyue Zhang¹, Shuping Zhang¹, Nannan Li¹, Yang Cao¹

Affiliations

¹ Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China.
² Guiyang Public Health Clinical Center(Internal Medicine Department three ward, Guiyang Public Health Clinical Center, Guiyang, 550004, Guizhou Province, People's Republic of China.).
³ Comprehensive Ward, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China.
⁴ Guiyang Public Health Clinical Center(The Department of Respiratory and Critical Medicine, Guiyang Public Health Clinical Center, Guiyang, 550004, Guizhou Province, People's Republic of China.).

PMID: 37608666
DOI: 10.2174/1386207326666230822122045

Abstract

Background: The abundance of circulating monocytes is closely associated with the development of atherosclerosis in humans.

Objective: This study aimed to further research into diagnostic biomarkers and targeted treatment of carotid atherosclerosis (CAS).

Methods: We performed transcriptomics analysis through weighted gene co-expression network analysis (WGCNA) of monocytes from patients in public databases with and without CAS. Differentially expressed genes (DEGs) were screened by R package limma. Diagnostic molecules were derived by the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithms. NetworkAnalyst, miRWalk, and StarBase databases assisted in the construction of diagnostic molecule regulatory networks. The DrugBank database predicted drugs targeting the diagnostic molecules. RT-PCR tested expression profiles.

Results: From 14,369 hub genes and 61 DEGs, six differentially expressed monocyte-related hub genes were significantly associated with immune cells, immune responses, monocytes, and lipid metabolism. LASSO and SVM-RFE yielded five genes for CAS prediction. RT-PCR of these genes showed HMGB1 was upregulated, and CCL3, CCL3L1, CCL4, and DUSP1 were down-regulated in CAS versus controls. Then, we constructed and visualized the regulatory networks of 9 transcription factors (TFs), which significantly related to 5 diagnostic molecules. About 11 miRNAs, 19 lncRNAs, and 39 edges centered on four diagnostic molecules (CCL3, CCL4, DUSP1, and HMGB1) were constructed and displayed. Eleven potential drugs were identified, including ibrutinib, CTI-01, roflumilast etc. Conclusion: A set of five biomarkers were identified for the diagnosis of CAS and for the study of potential therapeutic targets.

Keywords: Carotid atherosclerosis; Competing endogenous RNAs; Diagnosis; Monocytes; Potential drugs.