胃癌组织中雷帕霉素靶蛋白/70 ku核糖体蛋白S6激酶信号通路的表达及临床意义

Clinical significance of mammalian target of rapamycin/70 ku ribosomal protein S6 kinasesignal pathway in gastric carcinoma

目的 分析雷帕霉素靶蛋白（mTOR）、70 ku核糖体蛋白S6激酶（P70S6K）的表达水平与胃癌常见临床病理因素的关系.方法 采用逆转录聚合酶链反应技术,蛋白质印迹技术（Western-blot）检测32例胃癌患者癌组织、癌旁胃组织以及22例非胃癌患者胃组织中磷酸化雷帕霉素靶蛋白（mTOR）及磷酸化70 ku核酸体蛋白S6激酶（P70S6）K mRNA和蛋白水平的表达情况.结果 p-mTOR mRNA在胃癌组织中的表达水平（0.61±0.11）明显高于癌旁胃组织（0.43±0.10）及非胃癌胃组织（0.39 ±0.07）,p-P70S6KmRNA在胃癌组织中的表达水平（0.63 ±0.13）亦明显高于癌旁胃组织（0.45 ±0.14）及非胃癌胃组织（0.44±0.15）,差异均有统计学意义（均P＜0.05）;mTOR mRNA和P70S6K mRNA在胃癌组织中的表达呈正相关（r=0.521,P=0.033）;Western-blot检测结果也证实p-mTOR及p-P70S6K在胃癌组织中的表达高于癌旁胃组织及非胃癌胃组织;mTOR及P70S6K mRNA在胃癌组织中的表达水平与病理分期、淋巴结转移等明显相关,而与肿瘤直径、性别等无明显关系.结论 mTOR/P70S6K信号通路在胃癌组织中过度表达可能是胃癌发生的重要机制之一.

Objective To evaluate the mammalian target of rapamycin（mTOR）/70 ku ribosomal protein S6 kinase（P70S6K）in gastric carcinoma.Methods Reverse transcription-polymerase chain reaction and Western-blot were used to determine the expression of mTOR/P70S6K signaling pathway in cancerous and paracancerous tissues in 32 cases and 22 normal healthy tissues.Results The expression level of mTOR mRNA was markedly higher in the gastric carcinoma tissues（0.61 ± 0.11） than in the paracancerous tissues（0.43 ± 0.10） and normal stomach tissues（0.39 ± 0.07） ; the expression of P70S6K mRNA was also higher in the gastric carcinoma tissues （0.63 ± 0.13） than in the paracancerous tissues （0.45 ± 0.14） and normal stomach tissues （0.44 ±0.15）,with a significant difference among groups （P 〈0.05）.There was a positive correlation between mTOR mRNA and P70S6K mRNA expression in gastric carcinoma tissues（r =0.521,P =0.033）.Compared to those in other two groups,the protein expression of mTOR,P70S6K in gastric carcinoma were significantly increased.The expression of mTOR/P70S6K signaling pathway in the gastric carcinom tissues was significantly correlated with the pathological grading and lymph node metastasis,but not with the diameter and gender.Conclusions The mTOR/P70S6K signaling pathway is specifically activated in gastric carcinom tissues.The mTOR/P70S6K signaling pathway might play an important role in the pathogenesis of gastric carcinoma.