Potential Role of the Chemotaxis System in Formation and Progression of Intracranial Aneurysms Through Weighted Gene Co-Expression Network Analysis

Huaxin Zhu; Jiacong Tan; Yeyu Zhao; Zhihua Wang; Zhiwu Wu; Meihua Li

doi:10.2147/IJGM.S347420

Potential Role of the Chemotaxis System in Formation and Progression of Intracranial Aneurysms Through Weighted Gene Co-Expression Network Analysis

Int J Gen Med. 2022 Feb 27:15:2217-2231. doi: 10.2147/IJGM.S347420. eCollection 2022.

Authors

Huaxin Zhu¹, Jiacong Tan¹, Yeyu Zhao¹, Zhihua Wang¹, Zhiwu Wu¹, Meihua Li¹

Affiliation

¹ Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China.

Abstract

Background: Intracranial aneurysm (IA) is the most common and is the main cause of spontaneous subarachnoid hemorrhage (SAH). The underlying molecular mechanisms for preventing IA progression have not been fully identified. Our research aimed to identify the key genes and critical pathways of IA through gene co-expression networks.

Methods: Gene Expression Omnibus (GEO) datasets GSE13353, GSE54083 and GSE75436 were used in the study. The genetic data were analyzed by weighted gene co-expression network analysis (WGCNA). Then the clinically significant modules were identified and the differentially expressed genes (DEGs) with the genes were intersected in these modules. GO (gene ontology) and KEGG (Kyoto Gene and Genomic Encyclopedia) were used for gene enrichment analysis to determine the function or pathway. In addition, the composition of immune cells was analyzed by CIBERSORT algorithm. Finally, the hub genes and key genes were identified by GSE122897.

Results: A total of 266 DEGs and two modules with clinical significance were identified. The inflammatory response and immune response were identified by GO and KEGG. CCR5, CCL4, CCL20, and FPR3 were the key genes in the module correlated with IA. The proportions of infiltrating immune cells in IA and normal tissues were different, especially in terms of macrophages and mast cells.

Conclusion: The chemotactic system has been identified as a key pathway of IA, and interacting macrophages may regulate this pathological process.

Keywords: GEO; Gene Expression Omnibus; IA; WGCNA; chemotaxis; immune infiltration; intracranial aneurysm; weighted gene co-expression network analysis.

Grants and funding

This research was funded by the National Natural Science Foundation of China (NSFC) (No. 81860225), the key research and development plan of Jiangxi Province (No. 20203BBG73060), natural science foundation of Jiangxi Province (No. 20212BAB206029), and young talents research and cultivation foundation of the First Affiliated Hospital of Nanchang University (No. YFYPY202038).