Bioinformatic Identification of Differentially Expressed Genes and Pathways in Intracranial Aneurysm

Abstract

Background: Intracranial Aneurysm (IA) is a serious disease with high mortality and high morbidity rates, but the pathophysiological mechanisms of IA remain unclear. This study aimed to identify the Differentially Expressed Genes (DEGs) between IA tissues and Superficial Temporal Artery (STA) tissues using bioinformatic analysis. Methods: To investigate the key genes that are important for IAs, we analyzed microarray datasets (GSE75436) from the Gene Expression Omnibus (GEO) database, including 15 IA samples and 15 normal STA samples. First, we used the GEO2R tool to screen for DEGs (P-value<0.01 and |log2 FC| ≥2) between IA and STA tissues. Subsequently, the Database for Annotation, Visualization, and Integrated Discover software was used to perform function and pathway enrichment analyses. Finally, protein-protein interaction network analysis was performed using the Search Tool for Retrieval of Interacting Genes and Cytoscape software. Real-Time Quantitative Polymerase Chain Reaction (RT-QPCR) was performed to prove our assumption. Results: A total of 829 DEGs, of which 399 were upregulated and 430 were downregulated, were identified. The upregulated genes were mostly associated with Staphylococcus aureus infection, amoebiasis, rheumatoid arthritis, phagocytosis, and tuberculosis. The downregulated genes were mainly involved in vascular smooth muscle contraction, calcium signaling, histidine metabolism, cGMP-PKG signaling, and cAMP signaling. From the DEGs, five genes were selected as hub genes on the basis of the connection degree, which is one of 12 calculation methods from a plugin of Cytoscape called cytoHubba. The PCR results demonstrated that the expression levels of the top five hub genes, namely, Tumor Necrosis Factor (TNF), interleukin 8 (IL-8), Protein Tyrosine Phosphatase Receptor Type C (PTPRC), interleukin 1β (IL-1β), and Toll-like receptor 4 (TLR 4), were significantly higher in the IA samples than in the STA samples. Conclusion: TNF showed higher expression in the IA samples than in the STA samples. Thus, this gene may be involved in the occurrence and development of IA. The immune response and inflammation play important roles in the progression of IA. However, the specific pathophysiological mechanism needs further study.