Epithelial-to-mesenchymal transition predicts prognosis in clinical gastric cancer
Epithelial-to-mesenchymal transition predicts prognosis in clinical gastric cancer
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DOI：
10.1002/jso.23564
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发表时间：
2014-06-01
影响因子：
2.5
通讯作者：
Kodera, Yasuhiro
中科院分区：
文献类型：
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作者：
Murai, Toshifumi;Yamada, Suguru;Kodera, Yasuhiro
背景上皮间质转化（EMT）被认为在肿瘤的侵袭和转移中起重要作用。方法检测11株胃癌细胞系中上皮性标志物E-cadherin、间质性标志物vimentin和Zeb-1的mRNA水平。使用Zeb-1敲低进行功能分析。通过计算116例胃癌组织中vimentin/E-cadherin mRNA的表达比值，判断胃癌患者的EMT状态，并分析Zeb-1与EMT状态、临床病理因素、预后的相关性。结果细胞系分为上皮细胞系和间充质细胞系。Zeb-1表达与间充质表型显著相关。用Zeb-1 siRNA处理也降低了增殖、迁移和侵入的能力。根据V/E比值（vimentin/E-cadherin比值）将患者分为上皮性或间质性，并分为Zeb-1低表达组或高表达组。间质组与弥漫型癌症和IV期显著相关。多因素分析显示，EMT状态（间充质组）是独立的预后因素（P=0.022）。V/E比值与Zeb-1表达呈显著相关（r=0.73）。Zeb-1高表达组患者的生存率明显低于低表达组（P=0.0071）。结论EMT是影响胃癌预后的重要因素。Zeb-1可能是一个很有前途的治疗靶点。J. Surg. Oncol 2014; 109：684-689。(c)2014 Wiley Periodicals，Inc.
Background Epithelial-to-mesenchymal transition (EMT) is considered to play an important role in cancer invasion and metastasis. Methods The mRNA levels of an epithelial marker (E-cadherin), mesenchymal marker (vimentin), and Zeb-1 were measured in 11 gastric cancer cell lines. Functional analysis was performed using Zeb-1 knockdown. EMT status of 116 gastric cancer patients was determined by calculating the vimentin/E-cadherin mRNA expression ratio in cancerous tissue and the correlation between EMT status, clinicopathological factors, prognosis, and Zeb-1 were analyzed. Results Cell lines were classified as epithelial or mesenchymal. Zeb-1 expression was significantly correlated with the mesenchymal phenotype. Treatment with Zeb-1 siRNA also reduced the capacity to proliferate, migrate, and invade. Patients were classified as epithelial or mesenchymal by V/E ratio (vimentin/E-cadherin ratio) and as Zeb-1 low or high expression group. The mesenchymal group was significantly associated with diffuse type cancer and stage IV. On multivariate analysis, the EMT status (mesenchymal group) was an independent prognostic factor (P=0.022). There was a significant correlation between the V/E ratio and Zeb-1 expression (r=0.73). Patients in Zeb-1 high group had significantly poorer survival than those in low group (P=0.0071). Conclusions EMT is a critical prognostic factor for gastric cancer. Zeb-1 might be a promising therapeutic target. J. Surg. Oncol 2014; 109:684-689. (c) 2014 Wiley Periodicals, Inc.