Comprehensive Identification of Key Genes Involved in Development of Diabetes Mellitus-Related Atherogenesis Using Weighted Gene Correlation Network Analysis

Qi Huang; Guoxiong Deng; Rongguo Wei; Qiaoye Wang; Donghua Zou; Jinru Wei

doi:10.3389/fcvm.2020.580573

Comprehensive Identification of Key Genes Involved in Development of Diabetes Mellitus-Related Atherogenesis Using Weighted Gene Correlation Network Analysis

Front Cardiovasc Med. 2020 Oct 28:7:580573. doi: 10.3389/fcvm.2020.580573. eCollection 2020.

Authors

Qi Huang^{1

2}, Guoxiong Deng^{1

2}, Rongguo Wei^{3

4}, Qiaoye Wang^{5

6}, Donghua Zou^{5

6}, Jinru Wei^{1

2}

Affiliations

¹ Department of Cardiology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China.
² Department of Cardiology, The First People's Hospital of Nanning, Nanning, China.
³ Department of Clinical Laboratory, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China.
⁴ Department of Clinical Laboratory, The First People's Hospital of Nanning, Nanning, China.
⁵ Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China.
⁶ Department of Neurology, The First People's Hospital of Nanning, Nanning, China.

Abstract

Coronary heart disease (CHD) is common in patients with diabetes mellitus (DM), however, the relevant mechanism remains elusive. The whole blood gene expression profiles of healthy control, patients with DM, patients with DM and CHD (DMCHD) were used to performed weight gene correlation network analysis (WGCNA) to identify the gene modules associated with DM-related atherogenesis. The candidate module was significantly involved in immune- and T cell activity-related biological process. GSEA results suggested that lysosome and apoptosis were enriched in DM and DMCHD samples. The protein-protein-KEGG pathway network may reveal the potential transcriptional regulatory network involving in DM-related atherosclerosis. Nineteen genes (RTKN, DCP1B, PDZD4, CACNA2D2, TSEN54, PVRIG, PLEKHF1, NKG7, ZAP70, NUDCD3, SLAMF6, CCDC107, NAG6, ZDHHC14, EOMES, VIL2, WDR54, DMAP1, and PMPCA) were considered as DM-related atherogenesis genes (DRAGs). The Gene Set Variation Analysis (GSVA) score of the DRAG set gradually increased in the control, DM and DMCHD. ROC curve analysis showed that ZAP70, TSEN54, and PLEKHF1 may be potential blood circulation biomarkers for DMCHD in patients with DM. In conclusion, we identified nineteen hallmark genes involving in DM-related atherogenesis and constructed a potential transcriptional regulatory network involving in DM-related atherosclerosis.

Keywords: WGCNA; atherogenesis; coronary heart disease; diabetes mellitus; hallmark gene set.