Correlation of Delta-like Ligand 4 (DLL4) with VEGF and HIF-1α Expression in Human Glioma

To investigate the potential role of the notch ligand delta-like ligand 4 (DLL4) in glioma angiogenesis, weexamined whether its expression correlates with that of vascular endothelial growth factor (VEGF) and hypoxiainducedfactor-1α (HIF-1α). Eighty-two specimens of human glioma and 7 of normal brain tissue were subjectedto immunohistochemical analysis for DLL4, VEGF and HIF-1α expression. Statistical analysis were performedto determine if protein expression correlated with clinicopathological parameters, including histological type,pathological grade, and microvessel density (MVD), determined using CD34-labelling. Expression of DLL4,VEGF and HIF-1α was very strong in gliomas, relative to normal tissues, linked with the malignant grade.Moreover, DLL4 staining positively correlated with VEGF and HIF-1α expression and with MVD. Thus ourresults indicate that DLL4 represents a potential biomarker and therapeutic target for glioma angiogenesis.