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Research ArticleBrain

Correlation of Perfusion Parameters with Genes Related to Angiogenesis Regulation in Glioblastoma: A Feasibility Study

R. Jain, L. Poisson, J. Narang, L. Scarpace, M.L. Rosenblum, S. Rempel and T. Mikkelsen
American Journal of Neuroradiology August 2012, 33 (7) 1343-1348; DOI: https://doi.org/10.3174/ajnr.A2956
R. Jain
aFrom the Division of Neuroradiology, Departments of Radiology (R.J., J.N.)
bNeurosurgery (R.J., L.S., M.L.R., S.R., T.M.)
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L. Poisson
cPublic Health Sciences (L.P.), Henry Ford Health System, Detroit, Michigan.
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J. Narang
aFrom the Division of Neuroradiology, Departments of Radiology (R.J., J.N.)
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L. Scarpace
bNeurosurgery (R.J., L.S., M.L.R., S.R., T.M.)
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M.L. Rosenblum
bNeurosurgery (R.J., L.S., M.L.R., S.R., T.M.)
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S. Rempel
bNeurosurgery (R.J., L.S., M.L.R., S.R., T.M.)
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T. Mikkelsen
bNeurosurgery (R.J., L.S., M.L.R., S.R., T.M.)
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Abstract

BACKGROUND AND PURPOSE: Integration of imaging and genomic data is critical for a better understanding of gliomas, particularly considering the increasing focus on the use of imaging biomarkers for patient survival and treatment response. The purpose of this study was to correlate CBV and PS measured by using PCT with the genes regulating angiogenesis in GBM.

MATERIALS AND METHODS: Eighteen patients with WHO grade IV gliomas underwent pretreatment PCT and measurement of CBV and PS values from enhancing tumor. Tumor specimens were analyzed by TCGA by using Human Gene Expression Microarrays and were interrogated for correlation between CBV and PS estimates across the genome. We used the GO biologic process pathways for angiogenesis regulation to select genes of interest.

RESULTS: We observed expression levels for 92 angiogenesis-associated genes (332 probes), 19 of which had significant correlation with PS and 9 of which had significant correlation with CBV (P < .05). Proangiogenic genes such as TNFRSF1A (PS = 0.53, P = .024), HIF1A (PS = 0.62, P = .0065), KDR (CBV = 0.60, P = .0084; PS = 0.59, P = .0097), TIE1 (CBV = 0.54, P = .022; PS = 0.49, P = .039), and TIE2/TEK (CBV = 0.58, P = .012) showed a significant positive correlation; whereas antiangiogenic genes such as VASH2 (PS = −0.72, P = .00011) showed a significant inverse correlation.

CONCLUSIONS: Our findings are provocative, with some of the proangiogenic genes showing a positive correlation and some of the antiangiogenic genes showing an inverse correlation with tumor perfusion parameters, suggesting a molecular basis for these imaging biomarkers; however, this should be confirmed in a larger patient population.

ABBREVIATIONS:

FGF2
fibroblast growth factor 2
GBM
glioblastoma
GO
Gene Ontology
MMP1
matrix metallopeptidase 1 (interstitial collagenase)
PCT
perfusion CT
PS
permeability surface area product
TCGA
The Cancer Genome Atlas
TNF
tumor necrosis factor
VASH1
vasohibin 1
VE
vascular epithelium
VEGF
vascular endothelial growth factor
WHO
World Health Organization
  • © 2012 by American Journal of Neuroradiology
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American Journal of Neuroradiology: 33 (7)
American Journal of Neuroradiology
Vol. 33, Issue 7
1 Aug 2012
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R. Jain, L. Poisson, J. Narang, L. Scarpace, M.L. Rosenblum, S. Rempel, T. Mikkelsen
Correlation of Perfusion Parameters with Genes Related to Angiogenesis Regulation in Glioblastoma: A Feasibility Study
American Journal of Neuroradiology Aug 2012, 33 (7) 1343-1348; DOI: 10.3174/ajnr.A2956

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Correlation of Perfusion Parameters with Genes Related to Angiogenesis Regulation in Glioblastoma: A Feasibility Study
R. Jain, L. Poisson, J. Narang, L. Scarpace, M.L. Rosenblum, S. Rempel, T. Mikkelsen
American Journal of Neuroradiology Aug 2012, 33 (7) 1343-1348; DOI: 10.3174/ajnr.A2956
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