Identification of crucial genes in abdominal aortic aneurysm by WGCNA.

Siliang Chen,Dan Yang,Yuan Li,Xiao Wu,Chuxiang Lei,Xiaoning Sun,Yuehong Zheng,Mengyin Chen

doi:10.7717/peerj.7873

Abstract

BackgroundAbdominal aortic aneurysm (AAA) is the full thickness dilation of the abdominal aorta. However, few effective medical therapies are available. Thus, elucidating the molecular mechanism of AAA pathogenesis and exploring the potential molecular target of medical therapies for AAA is of vital importance.MethodsThree expression datasets (GSE7084, GSE47472 and GSE57691) were downloaded from the Gene Expression Omnibus (GEO). These datasets were merged and then normalized using the “sva” R package. Differential expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were conducted. We compared the co-expression patterns between AAA and normal conditions, and hub genes of each functional module were identified. DEGs were mapped to co-expression network under AAA condition and a DEG co-expression network was generated. Crucial genes were identified using molecular complex detection (MCODE) (a plugin in Cytoscape).ResultsIn our study, 6 and 10 gene modules were detected for the AAA and normal conditions, respectively, while 143 DEGs were screened. Compared to the normal condition, genes associated with immune response, inflammation and muscle contraction were clustered in three gene modules respectively under the AAA condition; the hub genes of the three modules were MAP4K1, NFIB and HPK1, respectively. A DEG co-expression network with 102 nodes and 303 edges was identified, and a hub gene cluster with 10 genes from the DEG co-expression network was detected. YIPF6, RABGAP1, ANKRD6, GPD1L, PGRMC2, HIGD1A, GMDS, MGP, SLC25A4 and FAM129A were in the cluster. The expression levels of these 10 genes showed potential diagnostic value.ConclusionBased on WGCNA, we detected 6 modules under the AAA condition and 10 modules in the normal condition. Hub genes of each module and hub gene clusters of the DEG co-expression network were identified. These genes may act as potential targets for medical therapy and diagnostic biomarkers. Further studies are needed to elucidate the detailed biological function of these genes in the pathogenesis of AAA.

Highlights

Abdominal aortic aneurysm (AAA) is a type of true aneurysm located at the abdominal aorta, and it is defined as permanent and irreversible dilation of the abdominal aorta to 50% more than the normal aortic diameter (Sakalihasan et al, 2018)
Elucidating the molecular mechanism of AAA pathogenesis and exploring the potential molecular targets of medical therapies for AAA is of vital importance
Abundant studies have been performed on the molecular mechanism of AAA pathogenesis (Golledge, 2019; Raffort et al, 2017; Sakalihasan et al, 2018), but weighted gene co-expression network analysis (WGCNA) has not been used to construct a gene co-expression network in AAA

Summary

Introduction

Abdominal aortic aneurysm (AAA) is a type of true aneurysm located at the abdominal aorta, and it is defined as permanent and irreversible dilation of the abdominal aorta to 50% more than the normal aortic diameter (Sakalihasan et al, 2018). Abundant studies have been performed on the molecular mechanism of AAA pathogenesis (Golledge, 2019; Raffort et al, 2017; Sakalihasan et al, 2018), but weighted gene co-expression network analysis (WGCNA) has not been used to construct a gene co-expression network in AAA. We compared the co-expression patterns between AAA and normal conditions, and hub genes of each functional module were identified. Hub genes of each module and hub gene clusters of the DEG co-expression network were identified. These genes may act as potential targets for medical therapy and diagnostic biomarkers.

Methods

Results

Conclusion