Crucial Gene Identification in Carotid Atherosclerosis Based on Peripheral Blood Mononuclear Cell (PBMC) Data by Weighted (Gene) Correlation Network Analysis (WGCNA)

Abstract

Background: Many patients are not responsive or tolerant to medical therapies for carotid atherosclerosis. Thus, elucidating the molecular mechanism for the pathogenesis and progression of carotid atherosclerosis and identifying new potential molecular targets for medical therapies that can slow progression of carotid atherosclerosis and prevent ischemic events are quite important. Material/Methods: We downloaded the expression profiling data of PBMC in Biobank of Karolinska Endarterectomy (BiKE, GSE21545) for GEO. The WGCNA and DEG screening were conducted. The co-expression pattern between patients with ischemic events (the events group) and patients without ischemic events (the no-events group) were compared. Then, we identified hub genes of each module. Finally, the DEG co-expression network was constructed and MCODE was used to identify crucial genes based on this co-expression network. Results: In the study, 183 DEGs were screened and 8 and 6 modules were assessed in the events group and no-events group, respectively. Compared to the no-events group, genes associated with inflammation and immune response were clustered in the green-yellow module of the events group. The hub gene of the green-yellow module of the events group was KIR2DL5A. We obtained 1 DEG co-expression network, which has 16 nodes and 24 edges, and we detected 5 crucial genes: SIRT1, THRAP3, RBM43, PEX1, and KLHDC2. The upregulated genes (THRAP3 and RBM43) showed potential diagnostic and prognostic value for the occurrence of ischemic events. Conclusions: We detected 8 modules for the events group and 6 modules for the no-events group. The hub genes for modules and crucial genes of the DEG co-expression network were also identified. These genes might serve as potential targets for medical therapies and biomarkers for diagnosis and prognosis. Further experimental and biological studies are needed to elucidate the role of these crucial genes in the progression of carotid atherosclerosis.

Correlation between Complement C1q A Chain (C1QA) and Macrophages in the Progression of Carotid Atherosclerosis

“…For example, Wang et al analyzed the GSE40231 dataset through WGCNA and determined the lncRNA that plays an important role in atherosclerosis ( 32 ). Siliang et al screened the key genes of carotid atherosclerosis in peripheral blood monocyte samples by WGCNA and DEG ( 33 ). In this study, two key modules of the CAS dataset GSE100927 and GSE43292 were analyzed by WGCNA.…”

Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532–3p Based on Bioinformatics Prediction and Validation

“…Carotid atherosclerotic is an important cause of stroke. Although fat, smoking, and chronic diseases are considered risk factors, the etiology of unstable plaque in carotid atherosclerotic is unclear owing to conflicting results ( Libby et al, 2019 ; Chen et al, 2020 ). Understanding the molecular mechanism underlying unstable plaque is of great importance for diagnosis and treatment.…”

Alteration in expression of matrix metalloproteinase-9 in peripheral blood mononuclear cells could be considered for estimating the severity of coronary artery stenosis

“…Peripheral blood mononuclear cells (PBMCs) expression analysis has recently been promoted as a diagnostic technique for determining the state of local and systemic inflammation. PBMCs are readily available reporter cells allowing identification of atherosclerosis events in early stages and can be considered an important candidate for novel therapeutic approaches (7)(8)(9)(10). As such, evaluating the cellular and molecular events in PBMCs via the progression of atherosclerosis has become a hot research topic in recent years.…”