环氧酶2、哺乳动物雷帕霉素靶蛋白及人类表皮生长因子受体2与胃癌预后的相关性

Association of cyclooxygenase 2, mammalian target of rapamycin and human epidermal growth factor receptor 2 with the prognosis of gastric carcinoma

目的：分析环氧酶2（COX-2）、哺乳动物雷帕霉素靶蛋白（mTOR）及人类表皮生长因子受体2（HER2/neu）与胃癌患者预后的相关性，为胃癌临床诊断和治疗提供实验依据。方法应用免疫组织化学染色方法对浙江省人民医院2008年4月至2010年4月期间诊治的80例胃癌患者手术样本进行分析，比较胃癌组织与癌旁正常胃组织中COX-2、mTOR及HER2/neu蛋白的表达差异。应用Spearman秩相关分析、Kaplan-Meier法、Log-rank检验以及多因素Cox风险比例回归模型描述和推断COX-2、mTOR及HER2/neu蛋白与胃癌病理分期及预后的相关关系。结果80份胃癌癌体组织样本中COX-2、mTOR、HER2/neu蛋白的阳性表达率分别为57.5%（46份）、36.3%（29份）和63.8%（51份），明显高于配对癌旁正常胃组织（u=5.643、3.528和4.642， P 均〈0.01）；COX-2和HER2/neu 蛋白表达水平和胃癌分期之间均呈正相关（rs=0.257、u=2.284， P〈0.05； rs=0.382、u=3.395，P〈0.01）；COX-2和HER2/neu蛋白阳性表达患者的总体生存情况和无复发生存情况明显劣于阴性表达患者（P均〈0.05）；COX-2蛋白的表达水平是胃癌总体生存时间的独立预测因素（风险比=1.643，95%CI：1.085~2.489，P〈0.05）。结论 COX-2、mTOR 和 HER2/neu 蛋白均参与了胃癌的发生或发展；COX-2和HER2/neu蛋白与胃癌的病理分期和总体生存时间相关；COX-2蛋白表达可作为胃癌预后的独立预测因子。

[Ab stract] Objective To investigate the correlation of cyclooxygenase 2 （COX-2）, mammalian target of rapamycin （mTOR） and human epidermal growth factor receptor 2 （HER2/neu） with prognosis of gastric carcinoma, in order to provide experimental basis for gastric carcinoma clinical diagnosis and treatment. Methods The gastric carcinoma tissue samples and matched adjacent normal tissue samples in 80 gastric carcinoma cases after surgery from April 2008 to April 2010 were all selected from Zhejiang Provincial People＇s Hospital. The differences in expression patterns of COX-2, mTOR and HER2/neu protein were compared. The correlation of COX-2, mTOR and HER2/neu protein with the clinical stage and prognosis of gastric carcinoma was described and assessed by Spearman rank correlation analysis, Kaplan-Meier method, long-rank test and Cox proportional hazards model. Results The expression rates of COX-2, mTOR and HER2/neu protein in 80 gastric carcinoma tissue samples were 57.5%（46 samples）, 36.3%（29 samples）和63.8%（51 samples）, which were all higher than adjacent normal tissue samples （u=5.643, 3.528 and 4.642, P all 〈0.01）. COX-2 and HER2/neu protein expressions were positively correlated with tumor stages of gastric carcinoma （rs=0.257, u=2.284, P〈0.05; rs=0.382, u=3.395,P〈0.01）. The overall survival rate and relapse-free survival rate of the patients with COX-2 and HER2/neu positive expression were inferior to negative ones （P all 〈0.05）. Furthermore, COX-2 expression was an independent prognostic factor for total survival time of gastric carcinoma （HR=1.643,95%CI： 1.085-2.489,P〈0.05）. Conclusions COX-2, mTOR and HER2/neu participate in the carcinogenesis of gastric carcinoma. COX-2 and HER2/neu are both progressive markers for gastric carcinoma, with COX-2 as an independent prognosticfactor for the prognosis of gastric carcinoma.