title: Glioblastoma: imaging genomic mapping reveals sex-specific oncogenic associations of cell death.
abstract: OBJECTIVE
  To identify the molecular profiles of cell death as defined by necrosis volumes at magnetic resonance (MR) imaging and uncover sex-specific molecular signatures potentially driving oncogenesis and cell death in glioblastoma (GBM).
  
  
  METHODS
  This retrospective study was HIPAA compliant and had institutional review board approval, with waiver of the need to obtain informed consent. The molecular profiles for 99 patients (30 female patients, 69 male patients) were identified from the Cancer Genome Atlas, and quantitative MR imaging data were obtained from the Cancer Imaging Archive. Volumes of necrosis at MR imaging were extracted. Differential gene expression profiles were obtained in those patients (including male and female patients separately) with high versus low MR imaging volumes of tumor necrosis. Ingenuity Pathway Analysis was used for messenger RNA-microRNA interaction analysis. A histopathologic data set (n = 368; 144 female patients, 224 male patients) was used to validate the MR imaging findings by assessing the amount of cell death. A connectivity map was used to identify therapeutic agents potentially targeting sex-specific cell death in GBM.
  
  
  RESULTS
  Female patients showed significantly lower volumes of necrosis at MR imaging than male patients (6821 vs 11 050 mm(3), P = .03). Female patients, unlike male patients, with high volumes of necrosis at imaging had significantly shorter survival (6.5 vs 14.5 months, P = .01). Transcription factor analysis suggested that cell death in female patients with GBM is associated with MYC, while that in male patients is associated with TP53 activity. Additionally, a group of therapeutic agents that can potentially be tested to target cell death in a sex-specific manner was identified.
  
  
  CONCLUSIONS
  The results of this study suggest that cell death in GBM may be driven by sex-specific molecular pathways.
authors.affiliation: From the Department of Radiology, University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1482, Houston, TX 77030 (R.R.C., J.W., S.K.S., P.O.Z.); Department of Biomedical Informatics, Emory University, Atlanta, Ga (D.A.G.); and Department of Neurosurgery, Baylor College of Medicine, Houston, Tex (P.O.Z.).
authors.forename: Rivka R
authors.initials: RR
authors.lastname: Colen
authors.forename: Jixin
authors.initials: J
authors.lastname: Wang
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Singh
authors.forename: David A
authors.initials: DA
authors.lastname: Gutman
authors.forename: Pascal O
authors.initials: PO
authors.lastname: Zinn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D016923:Cell Death / Q000235:genetics*; D002648:Child; D003287:Contrast Media; D005260:Female; D023281:Genomics / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012737:Sex Factors; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media