PT  - JOURNAL ARTICLE
AU  - W.B. Pope
AU  - L. Mirsadraei
AU  - A. Lai
AU  - A. Eskin
AU  - J. Qiao
AU  - H.J. Kim
AU  - B. Ellingson
AU  - P.L. Nghiemphu
AU  - S. Kharbanda
AU  - R.H. Soriano
AU  - S.F. Nelson
AU  - W. Yong
AU  - H.S. Phillips
AU  - T.F. Cloughesy
TI  - Differential Gene Expression in Glioblastoma Defined by ADC Histogram Analysis: Relationship to Extracellular Matrix Molecules and Survival
AID  - 10.3174/ajnr.A2917
DP  - 2012 Jun 01
TA  - American Journal of Neuroradiology
PG  - 1059--1064
VI  - 33
IP  - 6
4099  - http://www.ajnr.org/content/33/6/1059.short
4100  - http://www.ajnr.org/content/33/6/1059.full
SO  - Am. J. Neuroradiol.2012 Jun 01; 33
AB  - BACKGROUND AND PURPOSE: ADC histogram analysis can stratify outcomes in patients with GBM treated with bevacizumab. Therefore, we compared gene expression between high-versus-low ADC tumors to identify gene expression modules that could underlie this difference and impact patient prognosis. MATERIALS AND METHODS: Up-front bevacizumab-treated patients (N = 38) with newly diagnosed glioblastoma were analyzed by using an ADC histogram approach based on enhancing tumor. Using microarrays, we compared gene expression in high-versus-low ADC tumors in patients subsequently treated with bevacizumab. Tissue sections from a subset of tumors were stained for collagen and collagen-binding proteins. Progression-free and overall survival was determined by using Cox proportional hazard ratios and the Kaplan-Meier method with the log rank test. RESULTS: A total of 13 genes were expressed at 2-fold or greater levels in high- compared with low-ADC tumors at the P < .05 level. Of these, 6 encode for collagen or collagen-binding proteins. High gene expression for the collagen-binding protein decorin was associated with shorter survival (HR, 2.5; P = .03). The pattern and degree of collagen staining were highly variable in both high- and low-ADC tumors. CONCLUSIONS: High-ADC GBMs show greater levels of ECM protein gene expression compared with low-ADC GBMs. It is unclear whether this translates to the accumulation of higher levels of the encoded proteins. However, because ECM molecules could contribute to a proinvasive phenotype, this relationship merits further investigation. ADCLmean ADC (10−6 mm2/s) of the lower curve from the histogram analysisECMextracellular matrixGBMglioblastomaHRhazard ratioNIHNational Institutes of HealthRNAribonucleic acidRPArecursive partitioning analysisVEGFvascular endothelial growth factorVEGF-Avascular endothelial growth factor-A