Down-regulation of Nedd4L is Associated with the Aggressive Progression and Worse Prognosis of Malignant Glioma
Down-regulation of Nedd4L is Associated with the Aggressive Progression and Worse Prognosis of Malignant Glioma
复制标题
Nedd4L的下调与恶性胶质瘤的侵袭性进展和较差的预后相关
DOI：
10.1093/jjco/hyr195
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发表时间：
2012-03-01
影响因子：
2.4
通讯作者：
Tu, Yanyang
中科院分区：
文献类型：
--
作者：
He, Shiming;Deng, Jianping;Tu, Yanyang
人神经前体细胞表达的发育下调的4样蛋白（Nedd4L）是一种泛素蛋白连接酶，由多种癌细胞表达，可能具有致癌特性。其在胶质瘤组织中的表达模式尚不清楚。因此，我们认为，为探讨Nedd4L蛋白在胶质瘤中的表达及其与胶质瘤进展和预后的关系，采用免疫组化和western blot方法检测了128例胶质瘤中Nedd4L蛋白的表达，结果显示Nedd4L蛋白表达随胶质瘤病理分级的增高而增强，随着胶质瘤病理分级的增高而减弱（P 0.001），与western blot分析结果一致。此外，非参数分析显示，减弱的Nedd4L表达与较大的肿瘤直径（P 0.02）、较低的Karnofsky评分（P 0.008）、频繁的肿瘤内坏死（P 0.01）和较差的总生存期（P 0.009）显著相关。考克斯比例风险模型分析显示Nedd4L表达（P0.02）和肿瘤内坏死（P0.03）是两个重要的独立预后因素，本研究首次为Nedd4L在人脑胶质瘤中表达下调提供了有力证据。Nedd4L低表达的胶质瘤患者预后较差。
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.