EXPRESSION OF CRM1 IN HUMAN GLIOMAS AND ITS SIGNIFICANCE IN P27 EXPRESSION AND CLINICAL PROGNOSIS
EXPRESSION OF CRM1 IN HUMAN GLIOMAS AND ITS SIGNIFICANCE IN P27 EXPRESSION AND CLINICAL PROGNOSIS
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DOI：
10.1227/01.neu.0000348550.47441.4b
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发表时间：
2009-07-01
期刊：
影响因子：
4.8
通讯作者：
Cheng, Chun
中科院分区：
文献类型：
--
作者：
Shen, Aiguo;Wang, Yuchan;Cheng, Chun
目的：胶质瘤是颅内最常见的原发性肿瘤。虽然肿瘤分级可以预测大多数患者的临床病程，但个体肿瘤的分子特征已成为胶质瘤患者的重要预后因素。p27蛋白表达降低是多种癌症的独立预后标志物，与不良预后相关。据信，P27在Ser 10上的磷酸化已被证明是结合CRM 1（一种用于核输出的载体蛋白）所必需的。本研究评估是否CRM 1，Ser 10-磷酸化p27，p27相互关联，与胶质瘤病理分期，并与患者outcome.METHODS：免疫组化和Western blot分析70例人脑胶质瘤和正常脑组织。生存分析进行了使用Kaplan-Meier方法。结果：高CRM 1表达（80%的癌细胞核染色），观察70例，并与恶性程度。p27与Ser 10磷酸化p27（P < 0.001）和CRM 1（P < 0.001）呈负相关。我们还分别审查了每种级别的肿瘤，并调查了CRM 1表达是否预测了每个亚组中患者的生存率。结论：CRM 1和p27蛋白表达与胶质瘤分级有关，CRM 1蛋白高表达可能与预后不良有关。
OBJECTIVE: Gliomas are the most common type of primary intracranial tumor. Although tumor grade predicts the clinical course of most patients, molecular characteristics of individual tumors have emerged as important prognostic factors for patients with gliomas. Reduced expression of p27 protein is known as an independent prognostic marker in a large variety of cancers and is associated with an unfavorable prognosis. It is believed that phosphorylation of p27 on Ser10 has been shown to be required for the binding of CRM1, a carrier protein for nuclear export. This study assessed whether CRM1, Ser10-phosphorylated p27, and p27 correlated with each other, with glioma pathological stage, and with patient outcome.METHODS: Immunohistochemical and Western blot analysis were performed in 70 cases of human gliomas and normal brain tissues. Survival analyses were performed using the Kaplan-Meier method.RESULTS: High CRM1 expression (80% of cancer cell nuclei stained) was observed in 70 specimens and was related to the grade of malignancy. A strong inverse correlation was evident between p27 levels and both Ser10-phosphorylated p27 (P < 0.001) and CRM1 level (P < 0.001). We also reviewed each grade of tumors separately and investigated whether CRM1 expression predicted patient survival within each subgroup. In brief, CRM1 overexpression was significantly associated with overall survival (P < 0.001).CONCLUSION: The current results showed that CRM1 and p27 expression were associated with glioma grade and that high CRM1 protein expression might be related to poor outcome.