Identification of hub genes significantly linked to subarachnoid hemorrhage and epilepsy via bioinformatics analysis.

ABSTRACT

Background: Although epilepsy has been linked to subarachnoid hemorrhage (SAH), the underlying mechanism has not been fully elucidated. This study aimed to further explore the potential mechanisms in epilepsy and SAH through genes. Methods: Gene expression profiles for subarachnoid hemorrhage (GSE36791) and epilepsy (GSE143272) were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis was performed to identify the common differentially expressed genes (DEGs) to epilepsy and SAH, which were further analyzed by functional enrichment analysis. Single-sample gene set enrichment analysis (ssGSEA) and weighted correlation network analysis (WGCNA) were used to identify common module genes related to the infiltration of immune cells in epilepsy and SAH. Hub module genes were identified using a protein-protein interaction (PPI) network. Finally, the most relevant genes were obtained by taking the intersection points between the DEGs and hub module genes. We performed validation by retrospectively analyzing the RT-PCR levels of the most relevant genes in patients with pure SAH and patients with SAH complicated with epilepsy. Our experiments verified that the SAH and SAH+epilepsy groups were significantly different from the normal control group. In addition, significant differences were observed between the SAH and SAH+epilepsy groups. Results: In total, 159 common DEGs-85 downregulated genes and 74 upregulated genes-were identified. Functional analysis emphasized that the immune response was a common feature to epilepsy and SAH. The results of ssGSEA and WGCNA revealed changes in immunocyte recruitment and the related module genes. Finally, MMP9 and C3aR1 were identified as hub genes, and RT-PCR confirmed that the expression levels of the hub genes were higher in epilepsy and SAH samples than in normal samples. Conclusions: Our study revealed the pathogenesis of SAH complicated with epilepsy and identified hub genes that might provide new ideas for further mechanistic studies.