Comprehensive multiple molecular profile of epithelial mesenchymal transition in intrahepatic cholangiocarcinoma patients.
Comprehensive multiple molecular profile of epithelial mesenchymal transition in intrahepatic cholangiocarcinoma patients.
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肝内胆管癌患者上皮间质转化的综合多分子特征
DOI：
10.1371/journal.pone.0096860
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Huang XY;Zhang C;Cai JB;Shi GM;Ke AW;Dong ZR;Zhang PF;Fan J;Peng BG;Zhou J
本研究旨在探讨多种上皮间质转化(EMT)相关分子在肝内胆管细胞癌(ICC)中的表达及其预后意义。采用免疫组织化学方法检测E-钙粘蛋白、波形蛋白、蜗牛蛋白、Slug和β-catenin在14 0例根治性切除癌组织芯片中的表达。分析这些分子的表达与ICC患者临床病理特征的相关性，并评价其预后意义。E-钙粘蛋白表达降低和Vimentin表达增加，其特征性改变分别出现在55.0%和55.7%的原发ICC中，与ICC的淋巴转移和较差的总体生存期(OS)和无病生存期(DFS)相关。蜗牛蛋白和非膜性β-catenin在49.2%和45.7%的原代ICC中高表达，而在ICC中几乎不表达。胞浆/胞核β-catenin不能显著预测DFS的恶化，也与E-钙粘素丢失无关。Snail的过度表达预示着OS和DFS的恶化。蜗牛的过度表达与E-钙粘蛋白的下调和Vimentin的上调有关。Snail抑制ICC细胞株E-钙粘蛋白的表达，增强Vimentin的表达，损害ICC细胞的侵袭和迁移能力。这些数据支持内膜转移在肝细胞癌进展中起重要作用的假说，并提示蜗牛而不是鼻涕虫和β-连环蛋白在肝细胞癌内膜转移的诱导过程中起关键作用。
The aim of this study is to investigate the expression profile of multiple epithelial mesenchymal transition (EMT)-related molecules in intrahepatic cholangiocarcinoma (ICC) and the related prognostic significance. Immunohistochemistry was performed to determine the expression of E-cadherin, Vimentin, Snail, slug and β-catenin in a tissue microarray consisting of tumor tissues of 140 ICC patients undergoing curative resection. The correlation between the expression of these molecules and the clinicopathological characteristics of ICC patients was analyzed, and their prognostic implication was evaluated. Reduced E-cadherin and increased Vimentin expression, the characteristic changes of EMT, identified in 55.0% and 55.7% of primary ICCs, respectively, were correlated with lymphatic metastasis and poorer overall survival (OS) and disease-free survival (DFS) of ICCs. The overexpression of snail and nonmembranous β-catenin, which are the major regulators of the EMT, were identified in 49.2% and 45.7% of primary ICCs, while little slug expression was detected in ICCs. Cytoplasmic/nuclear β-catenin did not significantly predict worse DFS and was not related with E-cadherin loss. The overexpression of snail predicted worse OS and DFS. Snail overexpression correlated with the down-regulation of E-cadherin and the up-regulation of Vimentin. Inhibition of snail in an ICC cell line decreased the expression of E-cadherin, enhanced the expression of Vimentin and impaired the invasion and migration ability of ICC cells. These data support the hypothesis that EMT plays vital roles in ICC progression and suggest that snail but not slug and β-catenin plays a crucial role in the EMT induction of ICC.
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影响因子：
13.5
作者：
Wei, Y;Van Nhieu, JT;Buendia, MA
通讯作者：
Buendia, MA
影响因子：
50.3
作者：
Ansieau, Stephane;Bastid, Jeremy;Puisieux, Alain
通讯作者：
Puisieux, Alain
DOI：
10.1038/nrgastro.2011.20
发表时间：
2011-04
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
50.3
作者：
Moody, SE;Perez, D;Chodosh, LA
通讯作者：
Chodosh, LA
影响因子：
2.7
作者：
Brabletz, T;Hlubek, F;Kirchner, T
通讯作者：
Kirchner, T