PMID- 33765507
OWN - NLM
STAT- MEDLINE
DCOM- 20220329
LR  - 20240406
IS  - 1872-6844 (Electronic)
IS  - 0920-1211 (Print)
IS  - 0920-1211 (Linking)
VI  - 173
DP  - 2021 Jul
TI  - Analysis of intraoperative human brain tissue transcriptome reveals putative risk 
      genes and altered molecular pathways in glioma-related seizures.
PG  - 106618
LID - S0920-1211(21)00071-1 [pii]
LID - 10.1016/j.eplepsyres.2021.106618 [doi]
AB  - 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.
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Feyissa, Anteneh M
AU  - Feyissa AM
AD  - Department of Neurology, Mayo Clinic, Jacksonville, FL, USA. Electronic address: 
      Feyissa.Anteneh@mayo.edu.
FAU - Carrano, Anna
AU  - Carrano A
AD  - Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA.
FAU - Wang, Xue
AU  - Wang X
AD  - Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
FAU - Allen, Mariet
AU  - Allen M
AD  - Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
FAU - Ertekin-Taner, Nilufer
AU  - Ertekin-Taner N
AD  - Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
FAU - Dickson, Dennis W
AU  - Dickson DW
AD  - Department of Pathology, Mayo Clinic, Jacksonville, FL, USA.
FAU - Jentoft, Mark E
AU  - Jentoft ME
AD  - Department of Pathology, Mayo Clinic, Jacksonville, FL, USA.
FAU - Rosenfeld, Steven S
AU  - Rosenfeld SS
AD  - Department of Neurology, Mayo Clinic, Jacksonville, FL, USA; Department of 
      Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA; Department of 
      Pharmacology, Mayo Clinic, Jacksonville, FL, USA.
FAU - Tatum, William O
AU  - Tatum WO
AD  - Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
FAU - Ritaccio, Anthony L
AU  - Ritaccio AL
AD  - Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
FAU - Guerrero-Cazares, Hugo
AU  - Guerrero-Cazares H
AD  - Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA. Electronic 
      address: Cazares.Hugo@mayo.edu.
FAU - Quinones-Hinojosa, Alfredo
AU  - Quinones-Hinojosa A
AD  - Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA. Electronic 
      address: Quinones-Hinojosa.Alfredo@mayo.edu.
LA  - eng
GR  - R01 CA216855/CA/NCI NIH HHS/United States
GR  - R01 CA195503/CA/NCI NIH HHS/United States
GR  - R01 NS118513/NS/NINDS NIH HHS/United States
GR  - RF1 AG051504/AG/NIA NIH HHS/United States
GR  - U01 AG046139/AG/NIA NIH HHS/United States
GR  - P30 AG062677/AG/NIA NIH HHS/United States
GR  - R43 CA221490/CA/NCI NIH HHS/United States
GR  - R01 CA200399/CA/NCI NIH HHS/United States
GR  - R01 CA183827/CA/NCI NIH HHS/United States
GR  - R01 AG061796/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210318
PL  - Netherlands
TA  - Epilepsy Res
JT  - Epilepsy research
JID - 8703089
SB  - IM
MH  - Brain/pathology
MH  - Computational Biology
MH  - Gene Expression Profiling
MH  - *Glioma/complications/genetics/surgery
MH  - Humans
MH  - *Seizures/etiology/genetics
MH  - *Transcriptome
PMC - PMC9356713
MID - NIHMS1821474
OTO - NOTNLM
OT  - Brain tumor-related epilepsy
OT  - Cytokines
OT  - Epileptogenesis
OT  - Glioma-related seizures
OT  - Glutamatergic signaling
OT  - Immune-trafficking
OT  - Vesicular glutamate transporter
EDAT- 2021/03/26 06:00
MHDA- 2022/03/30 06:00
PMCR- 2022/08/06
CRDT- 2021/03/25 20:13
PHST- 2020/09/14 00:00 [received]
PHST- 2021/03/03 00:00 [revised]
PHST- 2021/03/16 00:00 [accepted]
PHST- 2021/03/26 06:00 [pubmed]
PHST- 2022/03/30 06:00 [medline]
PHST- 2021/03/25 20:13 [entrez]
PHST- 2022/08/06 00:00 [pmc-release]
AID - S0920-1211(21)00071-1 [pii]
AID - 10.1016/j.eplepsyres.2021.106618 [doi]
PST - ppublish
SO  - Epilepsy Res. 2021 Jul;173:106618. doi: 10.1016/j.eplepsyres.2021.106618. Epub 
      2021 Mar 18.