非小细胞肺癌中Twist通过TGF-β/Smad3信号通路促进EMT的发生

Twist induces epithelial-mesenchymal transition in NSCLC by regulating the TGF-β/Smad3 signaling pathway

目的:探讨非小细胞肺癌(NSCLC)组织转录因子Twist调控TGF-β/Smad3的表达,促进上皮间质转化(EMT)的发生机制。方法:采用免疫组织化学法检测NSCLC组织样本中Twist、TGF-β/Smad3以及EMT中代表性分子E-cadherin和Vimentin蛋白表达,并统计分析二者表达之间的相关性。结果:Twist、Smad3、Vimentin蛋白阳性着色定位于细胞质和细胞核内,Ecadherin蛋白阳性着色定位于细胞膜。Twist、Smad3、E-cadherin、Vimentin蛋白在NSCLC中阳性率分别为72.3%(120/166)、71.1%(118/166)、54.2%(90/166)、69.9%(116/166),显著高于癌旁组织,差异有统计学意义。Twist与Smad3、Smad3与E-cadherin、Vimentin在NSCLC不同分化程度及不同TNM分期均呈显著相关。结论:NSCLC中Twist可能通过TGF-β/Smad3信号通路促进EMT的发生。

Objective:To investigate the role of Twist which may induce EMT through TGF-β/Smad3 pathway in NSCLC,the expression of Twist,Smad3,E-cadherin and Vimentin molecules were detected and the correlations were discussed.Methods:Twist,Smad3,E-cadherin and Vimentin expressions in tumor tissues were assessed using immunohistochemical(IHC)methods in patients with resected NSCLC,and the correlation of Twist with Smad3,Smad3 with E-cadherin and Vimentin expression were analyzed.Results:The expression of Twist、Smad3、Vimentin were mainly located in cytoplasm and cell nucleus,and the expression of E-cadherin was mainly located on cell membrane.The positive expression rates of Twist,Smad3,E-cadherin and Vimentin protein in NSCLC were 72.3%(120/166),71.1%(118/166),54.2%(90/166),69.9%(116/166),which were higher than corresponding adjacent non-cancerous tissue with statistical difference(P<0.001).The correlation of Twist with Smad3,Smad3 with E-cadherin and Vimentin were obvious in pathological grads and TNM stages groups in NSCLC.Conclusion:Twist may induce EMT in NSCLC by regulating the TGF-β/Smad3 signaling pathway.