Tumor associated seizures in glioblastomas are influenced by survival gene expression in a region-specific manner: a gene expression imaging study

Epilepsy Res. 2014 Jul;108(5):843-52. doi: 10.1016/j.eplepsyres.2014.02.021. Epub 2014 Mar 12.

Abstract

Tumor associated seizures (TAS) are common and cause significant morbidity. Both imaging and gene expression features play significant roles in determining TAS, with strong interactions between them. We describe gene expression imaging tools which allow mapping of brain regions where gene expression has significant influence on TAS, and apply these methods to study 77 patients who underwent surgical evaluation for supratentorial glioblastomas. Tumor size and location were measured from MRI scans. A 9-set gene expression profile predicting long-term survivors was obtained from RNA derived from formalin-fixed paraffin embedded tissue. A total of 32 patients (42%) experienced preoperative TAS. Tumor volume was smaller (31.1 vs. 58.8 cubic cm, p<0.001) and there was a trend toward median survival being higher (48.4 vs. 32.7 months, p=0.055) in patients with TAS. Although the expression of only OLIG2 was significantly lower in patients with TAS in a groupwise analysis, gene expression imaging analysis revealed regions with significantly lower expression of OLIG2 and RTN1 in patients with TAS. Gene expression imaging is a powerful technique that demonstrates that the influence of gene expression on TAS is highly region specific. Regional variability should be evaluated with any genomic or molecular markers of solid brain lesions.

Keywords: Brain tumor; Gene expression; Imaging; Seizure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Brain / surgery
  • Brain Mapping / methods*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / physiopathology*
  • Brain Neoplasms / surgery
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression*
  • Glioblastoma / pathology
  • Glioblastoma / physiopathology*
  • Glioblastoma / surgery
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Oligodendrocyte Transcription Factor 2
  • Retrospective Studies
  • Seizures / pathology
  • Seizures / physiopathology*
  • Seizures / surgery
  • Survival Analysis
  • Survivors
  • Young Adult

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Nerve Tissue Proteins
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2
  • RTN1 protein, human