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[摘要]
目的: 探讨泛素结合酶UbcH10(ubiquitin-conjugating enzyme H10)蛋白在不同病理级别脑膜瘤组织中的表达及其临床意义。 方法: 选择2002年4月至2009年9月在长征医院神经外科手术治疗并经病理确诊、且临床随访资料完整的脑膜瘤患者47例,所有经诊断的颅内脑膜瘤病例均按2007年WHO分类标准分级,应用免疫组织化学方法研究UbcH10及Ki-67蛋白在不同病理级别脑膜瘤组织中的表达水平,并采用Spearman方法分析UbcH10与Ki-67蛋白表达的相关性。采用Kaplan-Meier法分析UbcH10表达与脑膜瘤无复发生存间的关系,以单因素和多因素回归模型分析UbcH10表达与脑膜瘤患者预后的关系,筛选影响预后的独立因素。 结果: UbcH10蛋白主要表达于脑膜瘤细胞核中,在脑膜瘤组织中阳性表达率显著高于正常脑组织\[(5.57±1.72)% vs 0,P=0.00\]。定量分析证实其在非典型性及间变型脑膜瘤中的表达水平明显高于典型性脑膜瘤\[(10.53±5.79)% vs (4.23±2.85)%,P<0.01\],提示UbcH10蛋白的表达与脑膜瘤病理分级有关。UbcH10表达与Ki-67蛋白的表达呈正相关(r=0.77,P<0.01)。Kaplan-Meier生存曲线结果显示,高UbcH10、Ki-67表达及高级别病理分级脑膜瘤患者相对于低UbcH10(P=0.007)、Ki-67表达(P=0.018)及低级别脑膜瘤病理分级患者无复发生存期显著缩短。Cox多因素分析显示,肿瘤病理分级(P=0.029)及UbcH10表达水平(P=0.044)为影响脑膜瘤患者预后的独立因素,风险比(hazard ratio,HR)分别为2.918和4.756。UbcH10过表达与脑膜瘤的复发明显相关,并且成为独立的预后因素,但还不能确定性别、年龄、Ki-67表达水平、肿瘤大小以及肿瘤位置对预后有影响。 结论: UbcH10可能参与了脑膜瘤的发生、发展过程,其表达情况可作为一个独立的风险评估指标预测脑膜瘤的预后。
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[Abstract]
Objective:To investigate the expression of ubiquitin-conjugating enzyme H10 (UbcH10) protein in meningiomas tissues of different pathological grades and its clinical significance. 〖WTHZ〗Methods:〖WTBZ〗Forty-seven patients diagnosed as meningioma with integrity clinical and follow-up information during April 2002 to September 2009 were selected from Department of Neurosurgery, Changzheng Hospital and were graded according to the 2007 WHO standard. The expressions of UbcH10 and Ki-67 proteins in meningioma tissues of various pathological grades were examined by immunohistochemistry. The correlation between the expressions of UbcH10 and Ki-67 protein was analyzed by using Spearman method. The correlation of UbcH10 expression with meningioma recurrence-free surivival was analyzed using the Kaplan-Meier method. 〖WTHZ〗Results:〖WTBZ〗UbcH10 protein was mainly expressed in the cytoplasm of meningioma cells. The expression of UbcH10 protein in meningioma tissues was significantly higher than that in normal brain tissues (\[5.57±1.72\]% vs 0,P=0.00). Quantitative analysis confirmed that the expression of UbcH10 protein was significantly higher in atypical and anaplastic meningiomas as compared with classic meningiomas (\[10.53±5.79\]% vs \[4.23±2.85\]%, P<0.01), indicating that the expression of UbcH10 protein was correlated with meningioma pathological grade and recurrence. The expression of UbcH10 protein was correlated with the expression of Ki-67 protein (r=0.77, P<0.01). Kaplan-Meier survival curve result indicated patients with high expression level of UbcH10 and Ki-67 and higher pathological grade showed a significantly shortened recurrence-free surivival than those with a lower expression level of UbcH10 (P=0.007) and Ki-67 (P=0.018), and a lower pathological grade (P<0.01). Cox multivariate regression analysis showed that the pathological grade (P=0.029) and the expression level of UbcH10 (P=0.044) were independent prognosis factors for meningioma patients, with the hazard ratio of 2.918 and 4756, respectively. Whereas, the clinicopathological factors, including age, gender, Ki-67 level, tumor diameter and tumor location were not independent factors for prognosis. Conclusion:UbcH10 may be involved in the development and progression of meningioma, and UbcH10 expression is an independent risk factor that could predict the prognosis.
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[基金项目]
上海市科学技术委员会基金资助项目(No. 08431900400)