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.