Relationship between gene expression and enhancement in glioblastoma multiforme: exploratory DNA microarray analysis.
OBJECTIVE
To determine the difference in gene expression between completely versus incompletely enhancing glioblastoma multiforme (GBM).


METHODS
Gene expression was determined for 52 newly diagnosed GBMs by using DNA microarrays, and the relationship to enhancement pattern and survival was analyzed. This study was approved by the institutional review board and was HIPAA compliant; informed consent was obtained.


RESULTS
Thirty-eight percent (20 of 52) of GBMs were incompletely enhancing (IE). The expression of eight genes was increased more than twofold in IE GBM when compared with completely enhancing (CE) GBM. Among these were tight junction protein-2 (2.2-fold increase, P = .019), and the oligodendroglioma markers oligodendrocyte lineage transcription factor 2 (2.4-fold increase, P = .029) and Achaete-scute complex-like 1 (ASCL1; 2.7-fold increase, P = .023). The expression of 71 genes showed relative overexpression in CE when compared with IE GBM. These included several proangiogenic and edema-related genes, including vascular endothelial growth factor (2.1-fold, P = .005) and neuronal pentraxin-2 (3.0-fold, P = .029). Several genes associated with primary GBM were overexpressed in CE tumors, whereas ASCL1, which is associated with secondary GBM, was overexpressed in IE tumors. Many genes overexpressed in IE GBM were associated with longer survival, whereas several genes overexpressed in CE GBM correlated with shortened survival.


CONCLUSIONS
The enhancement pattern divides GBM in two groups with differing prognoses. By comparing gene expression between IE and CE GBMs, it was possible to identify genes that may affect magnetic resonance imaging features of edema and enhancement, and genes whose expression levels are predictive of both improved and shortened survival.
Pope
Whitney B
WB
Department of Radiological Sciences, David Geffen School of Medicine at University of California-Los Angeles (UCLA) Medical Center, 10833 Le Conte Ave, BL-428/CHS, Los Angeles, CA 90095-1721, USA. wpope@mednet.ucla.edu
Chen
Jenny H
JH
Dong
Jun
J
Carlson
Marc R J
MR
Perlina
Alla
A
Cloughesy
Timothy F
TF
Liau
Linda M
LM
Mischel
Paul S
PS
Nghiemphu
Phioanh
P
Lai
Albert
A
Nelson
Stanley F
SF
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality; D002097:C-Reactive Protein / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D000076104:Oligodendrocyte Transcription Factor 2; D020411:Oligonucleotide Array Sequence Analysis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D062827:Zonula Occludens-2 Protein; D000099153:Pentraxins
D051792:Basic Helix-Loop-Helix Proteins; D002097:C-Reactive Protein; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D042461:Vascular Endothelial Growth Factor A; D062827:Zonula Occludens-2 Protein; D000099153:Pentraxins; C065500:ASCL1 protein, human; C405708:OLIG2 protein, human; C569046:TJP2 protein, human
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