Identification of Hub Genes Associated with the Pathogenesis of Intracranial Aneurysm via Integrated Bioinformatics Analysis

通过整合生物信息学分析鉴定与颅内动脉瘤发病机制相关的关键基因

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Abstract

BACKGROUND: At present, the pathogenesis of intracranial aneurysms (IA) remains unclear, which significantly hinders the development of novel strategies for the clinical treatment. In this study, bioinformatics methods were used to identify the potential hub genes and pathways associated with the pathogenesis of IA. METHODS: The gene expression datasets of patients with intracranial aneurysm were downloaded from the Gene Expression Database (GEO), and the different data sets were integrated by the robust rank aggregation (RRA) method to identify the differentially expressed genes between patients with intracranial aneurysm and the controls. The functional enrichment analyses of the significant differentially expressed genes (DEGs) were performed and the protein-protein interaction (PPI) network was constructed; thereafter, the hub genes were screened by cytoHubba plug-in of Cytoscape, and finally sequencing dataset GSE122897 was used to verify the hub genes. RESULTS: The GSE15629, GSE75436, GSE26969, and GSE6551 expression profiles have been included in this study, including 34 intracranial aneurysm samples and 26 control samples. The four datasets obtained 136 significant DEGs (45 up-regulated, 91 down-regulated). Enrichment analysis showed that the extracellular matrix structural constituent and the ECM-receptor interaction were closely related to the occurrence of IA. It was finally determined that eight hub genes associated with the development of IA, including VCAN, COL1A1, COL11A1, COL5A1, COL5A2, POSTN, THBS2, and CDH2. CONCLUSION: The discovery of potential hub genes and pathways could enhance the understanding of the molecular mechanisms associated with the development of IA. These hub genes may be potential therapeutic targets for the management and new biomarker for the diagnosis of IA.

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