Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA.
Epilepsy Res. 2021 Jul;173:106618. doi: 10.1016/j.eplepsyres.2021.106618. Epub 2021 Mar 18.
The pathogenesis of glioma-related seizures (GRS) is poorly understood. Here in, we aim to identify putative molecular pathways that lead to the development of GRS.
We determined brain transcriptome from intraoperative human brain tissue of patients with either GRS, glioma without seizures (non-GRS), or with idiopathic temporal lobe epilepsy (iTLE). We performed transcriptome-wide comparisons between disease groups tissue from non-epileptic controls (non-EC) to identify differentially-expressed genes (DEG). We compared DEGs to identify those that are specific or common to the groups. Through a gene ontology analysis, we identified molecular pathways enriched for genes with a Log-fold change ≥1.5 or ≤-1.5 and p-value <0.05 compared to non-EC.
We identified 110 DEGs that are associated with GRS vs. non-GRS: 80 genes showed high and 30 low expression in GRS. There was significant overexpression of genes involved in cell-to-cell and glutamatergic signaling (CELF4, SLC17A7, and CAMK2A) and down-regulation of genes involved immune-trafficking (CXCL8, H19, and VEGFA). In the iTLE vs GRS analysis, there were 1098 DEGs: 786 genes were overexpressed and 312 genes were underexpressed in the GRS samples. There was significant enrichment for genes considered markers of oncogenesis (GSC, MYBL2, and TOP2A). Further, there was down-regulation of genes involved in the glutamatergic neurotransmission (vesicular glutamate transporter-2) in the GRS vs. iTLE samples.
We identified a number of altered processes such as cell-to-cell signaling and interaction, inflammation-related, and glutamatergic neurotransmission in the pathogenesis of GRS. Our findings offer a new landscape of targets to further study in the fields of brain tumors and seizures.
胶质瘤相关癫痫（GRS）的发病机制尚不清楚。在此，我们旨在确定导致 GRS 发生的潜在分子途径。
我们从患有 GRS、无癫痫发作的胶质瘤（非 GRS）或特发性颞叶癫痫（iTLE）的患者的术中脑组织中确定了大脑转录组。我们将疾病组与非癫痫对照组（非 EC）的组织进行全转录组比较，以确定差异表达基因（DEG）。我们比较了 DEG，以确定那些对组特异或共同的基因。通过基因本体分析，我们确定了与 Log 倍变化≥1.5 或≤-1.5 且与非 EC 相比 p 值<0.05 的基因相关的分子途径。
我们确定了 110 个与 GRS 与非 GRS 相关的 DEG：80 个基因在 GRS 中高表达，30 个基因低表达。涉及细胞间和谷氨酸能信号的基因显著过表达（CELF4、SLC17A7 和 CAMK2A），而参与免疫运输的基因下调（CXCL8、H19 和 VEGFA）。在 iTLE 与 GRS 的分析中，有 1098 个 DEG：在 GRS 样本中，786 个基因过表达，312 个基因低表达。被认为是致癌标志物的基因显著富集（GSC、MYBL2 和 TOP2A）。此外，在 GRS 与 iTLE 样本中，谷氨酸能神经递质（囊泡谷氨酸转运体-2）的基因下调。
我们确定了一些改变的过程，如细胞间信号转导和相互作用、炎症相关和谷氨酸能神经递质在 GRS 发病机制中的作用。我们的发现为肿瘤和癫痫领域的进一步研究提供了新的靶点。
