Analysis of intraoperative human brain tissue transcriptome reveals putative risk genes and altered molecular pathways in glioma-related seizures

Anteneh M. Feyissa, Anna Carrano, Xue Wang, Mariet Allen, Nilüfer Ertekin-Taner, Dennis W. Dickson, Mark E. Jentoft, Steven S. Rosenfeld, William O. Tatum, Anthony L. Ritaccio, Hugo Guerrero Cázares, Alfredo Quiñones-Hinojosa

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Article number106618
JournalEpilepsy Research
Volume173
DOIs
StatePublished - Jul 2021

Keywords

  • Brain tumor-related epilepsy
  • Cytokines
  • Epileptogenesis
  • Glioma-related seizures
  • Glutamatergic signaling
  • Immune-trafficking
  • Vesicular glutamate transporter

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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