title: Correlation of high delta-like ligand 4 expression with peritumoral brain edema and its prediction of poor prognosis in patients with primary high-grade gliomas.
abstract: OBJECTIVE
  Peritumoral brain edema (PTBE) is a common phenomenon associated with high-grade gliomas (HGGs). In this study, the authors investigated the expression of Notch delta-like ligand 4 (DLL4) and its correlation with PTBE and prognosis in patients with an HGG.
  
  
  METHODS
  Tumors from 99 patients with HGG were analyzed for DLL4 expression using immunohistochemistry. PTBE on preoperative MR images and the relationship between PTBE and DLL4 expression were evaluated. The effect of DLL4 on patient prognosis was assessed by using Kaplan-Meier survival and Cox proportional hazard models.
  
  
  RESULTS
  Immunohistochemistry results revealed that the expression of DLL4 was distributed primarily within the cytoplasm of tumor vascular endothelial cells and seldom detected in tumor cells. DLL4 expression was correlated positively with the degree of edema (r = 0.845 and p < 0.001, Spearman's test). In addition, DLL4 was an independent predictor of prognosis in patients with HGGs (p = 0.001).
  
  
  CONCLUSIONS
  DLL4 expression was correlated positively with the degree of PTBE and was an independent unfavorable prognostic indicator in patients with HGG.
authors.affiliation: Tumor Invasion Micro-ecological Laboratory, Fujian Medical University; and |Departments of 2 Neurosurgery and.
authors.forename: Xian-Xin
authors.initials: XX
authors.lastname: Qiu
authors.affiliation: Tumor Invasion Micro-ecological Laboratory, Fujian Medical University; and 
authors.forename: Chen-Hong
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Tumor Invasion Micro-ecological Laboratory, Fujian Medical University; and |Departments of 2 Neurosurgery and.
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Lin
authors.affiliation: Tumor Invasion Micro-ecological Laboratory, Fujian Medical University; and 
authors.forename: Na
authors.initials: N
authors.lastname: You
authors.affiliation: Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Xing-Fu
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Tumor Invasion Micro-ecological Laboratory, Fujian Medical University; and 
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.affiliation: Tumor Invasion Micro-ecological Laboratory, Fujian Medical University; and 
authors.forename: Shui-Yuan
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Departments of 2 Neurosurgery and.
authors.forename: De-Zhi
authors.initials: DZ
authors.lastname: Kang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001929:Brain Edema / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D001932:Brain Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005910:Glioma / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C064045:delta protein
keywords: DLL4 = delta-like ligand 4; HGG = high-grade glioma; HR = hazard ratio; MGMT = O6-methylguanine-DNA methyltransferase; Notch delta-like ligand 4; OS = overall survival; PBS = phosphate-buffered saline; PI = positive index; PTBE = peritumoral brain edema; T2WI = T2-weighted image; TTP = time to progression; VEGF = vascular endothelial growth factor; high-grade glioma; peritumoral brain edema