The potential role of chemotaxis and the complement system in the formation and progression of thoracic aortic aneurysms inferred from the weighted gene coexpression network analysis

Chuxiang Lei,Wei Wang,Yuehong Zheng,Dan Yang,Hui Zhang,Haoxuan Kan,Lei Ji,Wenlin Chen,Fang Xu

doi:10.1186/s12967-021-02716-6

Abstract

BackgroundThoracic aortic aneurysm (TAA) can be life-threatening due to the progressive weakening and dilatation of the aortic wall. Once the aortic wall has ruptured, no effective pharmaceutical therapies are available. However, studies on TAA at the gene expression level are limited. Our study aimed to identify the driver genes and critical pathways of TAA through gene coexpression networks.MethodsWe analyzed the genetic data of TAA patients from a public database by weighted gene coexpression network analysis (WGCNA). Modules with clinical significance were identified, and the differentially expressed genes (DEGs) were intersected with the genes in these modules. Gene Ontology and pathway enrichment analyses were performed. Finally, hub genes that might be driving factors of TAA were identified. Furthermore, we evaluated the diagnostic accuracy of these genes and analyzed the composition of immune cells using the CIBERSORT algorithm.ResultsWe identified 256 DEGs and two modules with clinical significance. The immune response, including leukocyte adhesion, mononuclear cell proliferation and T cell activation, was identified by functional enrichment analysis. CX3CR1, C3, and C3AR1 were the top 3 hub genes in the module correlated with TAA, and the areas under the curve (AUCs) by receiver operating characteristic (ROC) analysis of all the hub genes exceeded 0.7. Finally, we found that the proportions of infiltrating immune cells in TAA and normal tissues were different, especially in terms of macrophages and natural killer (NK) cells.ConclusionChemotaxis and the complement system were identified as crucial pathways in TAA, and macrophages with interactive immune cells may regulate this pathological process.

Highlights

Aortic aneurysm is a common vascular disease defined as aortic enlargement or expansion with an artery diameter > 1.5 times the average [1]
To further investigate the biological behaviors of these differentially expressed genes (DEGs), we performed enrichment analysis on Gene Ontology (GO) (Fig. 2c) and Kyoto Encyclopedia of Genes and Genomes (KEGG) (Fig. 2d) gene sets (GO and KEGG ids and other detailed information are provided in the supplementary materials, Additional file 3: Table S2)
According to the enrichment analysis, regulation of the immune effector process, cell–cell adhesion, immune cell proliferation, and immune receptor activity were most significantly enriched, suggesting that the immune process might play an essential role in Thoracic aortic aneurysm (TAA) formation and

Summary

Introduction

Aortic aneurysm is a common vascular disease defined as aortic enlargement or expansion with an artery diameter > 1.5 times the average [1]. Thoracic aortic aneurysm (TAA), characterized by a weakening and. TAA can be a potentially lifethreatening condition due to rupture because of its expansion and progression characteristics. Abdominal aortic aneurysm (AAA), another aortic aneurysmal disease with an incidence rate of up to 1% ~ 2% among men aged ≥ 65 years [2], shares several but limited common clinical and pathological characteristics with TAA [3]. There are fewer previous studies related to the pathological mechanisms of TAA than AAA, regardless of the notable differences between these two diseases. Thoracic aortic aneurysm (TAA) can be life-threatening due to the progressive weakening and dilatation of the aortic wall. Our study aimed to identify the driver genes and critical pathways of TAA through gene coexpression networks

Methods

Results

Discussion

Conclusion