哺乳动物雷帕霉素靶蛋白信号通路及其下游蛋白在胃癌组织中的活化及临床意义  

Activation and its clinical significance of the mammalian target of rapamycin pathway and its downstream proteins in gastric cancer

作　　者：孙丹凤[1,2] 张燕捷[3] 田筱青[1,2] 房静远[1,2] 

机构地区：[1]上海交通大学医学院附属仁济医院消化科,上海200001 [2]上海市消化疾病研究所,上海200001 [3]上海交通大学医学院附属第三人民医院消化科,上海200001

出　　处：《中华消化杂志》2013年第3期166-170,共5页Chinese Journal of Digestion

基　　金：国家自然科学基金青年科学基金（81001070）

摘　　要：目的研究哺乳动物雷帕霉素靶蛋白（mTOR）信号通路相关蛋白mTOR和真核起始因子4E结合蛋白1（4E-BP1）在胃癌组织中的活化情况及其临床意义。方法利用免疫组织化学技术观察38例手术患者胃癌组织中mTOR和4E-BP1的活化情况，采用卡方检验及Kruskal-Wallis检验分析磷酸化mTOR及4E-BP1在癌区、癌旁和正常胃黏膜组织中表达的差异，以及各种临床病理参数间的表达差异。结果磷酸化mTOR在胃癌组织中的阳性表达率高于匹配的癌旁及正常组织[71.1％（27／38）比50.0％（19／38）比44.7％（17／38）；X^2=11.031，P=0.026]，其下游的4E-BP1在胃癌组织中的阳性表达率也高于匹配的癌旁及正常组织[68.4％（26／38）比57.9％（22／38）比28.9％（11／38）；X^2=13.943，P=0.007]。磷酸化mTOR和4E-BP1与肿瘤Lauren＇s分型、浸润分期、分化程度、淋巴结转移及患者年龄等无关，但胃癌组织中活化的4E-BP1在不同大小肿瘤间表达差异有统计学意义（H=3.86，P〈0.05）。结论mTOR信号通路在胃癌发生中存在过度激活，其下游蛋白4e-BP1磷酸化程度在不同大小肿瘤中存在差异。Objective To investigate the activation and clinical significance of the mammalian target of rapamycin （mTOR） pathway related protein and eukaryotic translation factor 4E-binding protein 1 （4E-BP1） in gastric cancer. Methods The activation of roTOR and 4E-BP1 in gastric cancer tissues of 38 surgical patients were detected by immunohistochemical method. The differences of phosphorylated mTOR and 4E-BP1 expression among cancerous tissues, para-cancerous tissues and normal gastric mucosa tissues and dinicopathological variables were analyzed by Chi square test and Kruskal-Wallis test. Results The positive expression rate of phosphorylated mTOR in the gastric cancerous tissues was significantly higher than that of para-cancerous tissues and normal tissues [71.1% （27/ 38）, 50.0%（19/38） and 44.7% （17/38）, X^2 = 11.031, P= 0.026]. The positive expression rate of downstream protein 4E-BP1 in the gastric cancer tissues was also significantly higher than that of para- cancerous tissues and normal tissues [68.40%（26/38）, 57.9%（22/38） and 28.9%（11/38）,X^2=13.943, P=0.007]. There was no correlation between phosphorylated roTOR and 4E-BP1 expression and tumor Lauren＇s sub-type, infiltration, differentiation degree, lymph node metastasis and patient＇s age. There was statistical significant difference between activated 4E-BP1 expression and tumor size in gastric cancer （H=3.86, P〈0.05）. Conclusions mTOR pathway was over activated in gastric cancer. There was difference between phosphorylation degree of its downstream protein 4E-BP1 and the tumor size.

关 键 词：西罗莫司 蛋白质丝氨酸苏氨酸激酶 信号转导 真核细胞起始因子4E 胃肿瘤 

分 类 号：R735.2[医药卫生—肿瘤]