UNASSIGNED: To screen out candidate genes associated with CAD in non-diabetic patients, weighted gene co-expression network analysis (WGCNA) was constructed to conduct an analysis of microarray expression profiling in patients with CAD. First, the microarray data GSE20680 and GSE20681 were downloaded from NCBI. We constructed co-expression modules via WGCNA after excluding the diabetic patients. As a result, 18 co-expression modules were screened out, including 1,225 differentially expressed genes (DEGs) that were obtained from 152 patients (luminal stenosis ≥50% in at least one major vessel) and 170 patients (stenosis of <50%). Subsequently, a Pearson\'s correlation analysis was conducted between the modules and clinical traits. Then, a functional enrichment analysis was conducted, and we used gene network analysis to reveal hub genes. Last, we validated the hub genes with peripheral blood samples in an independent patient cohort using RT-qPCR.
UNASSIGNED: The results showed that the midnight blue module and the yellow module played vital roles in the pathogenesis of CAD in non-diabetic patients. Additionally, CD40, F11R, TNRC18, and calcium/calmodulin-dependent protein kinase type II gamma (CAMK2G) were screened out and validated using enzyme-linked immunosorbent assay (ELISA) in an independent patient cohort and immunohistochemical (IHC) staining in an atherosclerosis mouse model.
UNASSIGNED: Our findings demonstrate that hub genes, CD40, F11R, TNRC18, and CAMK2G, are surrogate diagnostic biomarkers and/or therapeutic targets for CAD in non-diabetic patients and require deeper validation.