Chuxiang Lei1, Dan Yang2, Wenlin Chen3, Haoxuan Kan1, Fang Xu1, Hui Zhang1, Wei Wang1, Lei Ji1, Yuehong Zheng4. 1. Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No 1. Shuaifuyuan, Dongcheng District, Beijing, China. 2. Department of Computational Biology and Bioinformatics, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 3. Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 4. Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No 1. Shuaifuyuan, Dongcheng District, Beijing, China. yuehongzheng@yahoo.com.
Abstract
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.
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.
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