title: High delta-like ligand 4 (DLL4) is correlated with peritumoral brain edema and predicts poor prognosis in primary glioblastoma.
abstract: Delta-like ligand 4 (DLL4), 1 of the 5 known Notch ligands, is involved in a variety of tumor initiation and progression, particularly in the process of tumor angiogenesis. However, the clinical and prognostic significance of DLL4 in glioblastoma have not been fully elucidated.Tumor tissues from 69 glioblastoma patients were analyzed using immunohistochemistry for DLL4 expression. Peritumoral brain edema (PTBE) on preoperative magnetic resonance imaging of these patients and the relationship with DLL4 expression were evaluated. The effect on prognosis was assessed by using the Kaplan-Meier survival and the Cox proportional hazard model.The results showed that elevated DLL4 expression was primarily distributed in the cytoplasm of tumor vascular endothelial cells and rarely detected in tumor cells. Univariate analysis indicated significant correlation of high DLL4 expression with shorter time to progression (TTP) (P < 0.001) and overall survival (OS) (P < 0.001) in glioblastoma. Multivariate analysis confirmed high DLL4 expression as an unfavorable prognostic indicator for TTP (P < 0.001) and OS (P < 0.001), independent of age, gender, symptom duration, resection degree, and PTBE. Importantly, the study also found that DLL4 expression was positively related with PTBE (Spearman's test: r = 0.845, P < 0.001). A multiple linear regression model was constructed to confirm that the positive index of DLL4 was associated with an increase in maximum extent of PTBE (P < 0.001).It is thus concluded that DLL4 is correlated with PTBE and may be useful for predicting prognosis in glioblastoma.
authors.affiliation: Department of Neurosurgery (XQ, ZL, CZ, SL), First Affiliated Hospital, Fujian Medical University; Tumor Invasion Micro-Ecological Laboratory (LC, CW, ZL), Fujian Medical University; and Department of Pathology (XW, YC), First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Xian-Xin
authors.initials: XX
authors.lastname: Qiu
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.forename: Chen-Hong
authors.initials: CH
authors.lastname: Wang
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Lin
authors.forename: Chang-Fu
authors.initials: CF
authors.lastname: Zhou
authors.forename: Shui-Yuan
authors.initials: SY
authors.lastname: Liu
authors.forename: Xing-Fu
authors.initials: XF
authors.lastname: Wang
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D001929:Brain Edema / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000401:mortality* / Q000473:pathology; D002135:Calcium-Binding Proteins; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000401:mortality* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D036341:Intercellular Signaling Peptides and Proteins