Gao Hong, Li Jie, Li Qiuping, Lin Yuanxiang
Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Department of Neurosurgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian, China.
Front Neurol. 2023 Jan 19;14:1061860. doi: 10.3389/fneur.2023.1061860. eCollection 2023.
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.
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.
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.
Our study revealed the pathogenesis of SAH complicated with epilepsy and identified hub genes that might provide new ideas for further mechanistic studies.
尽管癫痫已被认为与蛛网膜下腔出血（SAH）有关，但其潜在机制尚未完全阐明。本研究旨在通过基因进一步探索癫痫与SAH之间的潜在机制。
从基因表达综合数据库（GEO）下载蛛网膜下腔出血（GSE36791）和癫痫（GSE143272）的基因表达谱。进行差异表达分析以鉴定癫痫和SAH的共同差异表达基因（DEG），并通过功能富集分析进一步分析这些基因。使用单样本基因集富集分析（ssGSEA）和加权相关网络分析（WGCNA）来鉴定与癫痫和SAH中免疫细胞浸润相关的共同模块基因。使用蛋白质-蛋白质相互作用（PPI）网络鉴定枢纽模块基因。最后，通过取DEG与枢纽模块基因的交点获得最相关的基因。我们通过回顾性分析纯SAH患者和SAH合并癫痫患者中最相关基因的RT-PCR水平进行验证。我们的实验证实，SAH组和SAH +癫痫组与正常对照组有显著差异。此外，SAH组和SAH +癫痫组之间也观察到显著差异。
共鉴定出159个共同的DEG，其中85个下调基因和74个上调基因。功能分析强调免疫反应是癫痫和SAH的共同特征。ssGSEA和WGCNA的结果揭示了免疫细胞募集和相关模块基因的变化。最后，鉴定出MMP9和C3aR1为枢纽基因，RT-PCR证实癫痫和SAH样本中枢纽基因的表达水平高于正常样本。
我们的研究揭示了SAH合并癫痫的发病机制，并鉴定出枢纽基因，这可能为进一步的机制研究提供新思路。
