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.
Chemotaxis
Immune infiltration
Thoracic aortic aneurysm
Weighted gene coexpression network analysis
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
02 02 2021
02 02 2021
Historique:
received:
20
11
2020
accepted:
23
01
2021
entrez:
3
2
2021
pubmed:
4
2
2021
medline:
15
5
2021
Statut:
epublish
Résumé
Thoracic 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. We 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. We 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. Chemotaxis and the complement system were identified as crucial pathways in TAA, and macrophages with interactive immune cells may regulate this pathological process.
Sections du résumé
BACKGROUND
Thoracic 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.
METHODS
We 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.
RESULTS
We 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.
CONCLUSION
Chemotaxis and the complement system were identified as crucial pathways in TAA, and macrophages with interactive immune cells may regulate this pathological process.
Identifiants
pubmed: 33531038
doi: 10.1186/s12967-021-02716-6
pii: 10.1186/s12967-021-02716-6
pmc: PMC7852290
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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