title: Differential gene expression in glioblastoma defined by ADC histogram analysis: relationship to extracellular matrix molecules and survival.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1721, USA. wpope@mednet.ucla.edu
authors.forename: W B
authors.initials: WB
authors.lastname: Pope
authors.forename: L
authors.initials: L
authors.lastname: Mirsadraei
authors.forename: A
authors.initials: A
authors.lastname: Lai
authors.forename: A
authors.initials: A
authors.lastname: Eskin
authors.forename: J
authors.initials: J
authors.lastname: Qiao
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: B
authors.initials: B
authors.lastname: Ellingson
authors.forename: P L
authors.initials: PL
authors.lastname: Nghiemphu
authors.forename: S
authors.initials: S
authors.lastname: Kharbanda
authors.forename: R H
authors.initials: RH
authors.lastname: Soriano
authors.forename: S F
authors.initials: SF
authors.lastname: Nelson
authors.forename: W
authors.initials: W
authors.lastname: Yong
authors.forename: H S
authors.initials: HS
authors.lastname: Phillips
authors.forename: T F
authors.initials: TF
authors.lastname: Cloughesy
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014018:Tissue Distribution
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D000068258:Bevacizumab