Down-regulation of Nedd4L is Associated with the Aggressive Progression and Worse Prognosis of Malignant Glioma

Abstract

Human neural precursor cell-expressed developmentally down-regulated 4 like (Nedd4L), a ubiquitin protein ligase, is expressed by various cancer cells and might have an oncogenic property. Its expression pattern in glioma tissues is unknown. Therefore, the aim of this study was to investigate whether Nedd4L is present in glioma and to evaluate the correlation of Nedd4L expression with the progression and prognosis of the disease. Immunohistochemistry and western blot were used to investigate the expression of Nedd4L protein in 128 patients with gliomas. Immunohistochemistry showed a strong-to-weak range of Nedd4L staining with increasing pathologic grade of glioma (P < 0.001), which was in line with the results from western blot analysis. In addition, a non-parametric analysis revealed that the attenuated Nedd4L expression was significantly correlated with a large tumor diameter (P = 0.02), low Karnofsky performance score (P = 0.008), frequent intra-tumor necrosis (P = 0.01) and worse overall survival (P = 0.009). Furthermore, multivariate analysis showed that Nedd4L expression (P = 0.02) and intra-tumor necrosis (P = 0.03) were two important independent prognostic factors identified by the Cox proportional hazards model. Our results provide convincing evidence for the first time that the expression of Nedd4L is down-regulated in human gliomas. The glioma patients with lower Nedd4L expression have a worse prognosis.