Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
J Surg Oncol. 2014 Jun;109(7):684-9. doi: 10.1002/jso.23564. Epub 2014 Jan 22.
Epithelial-to-mesenchymal transition (EMT) is considered to play an important role in cancer invasion and metastasis.
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.
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).
EMT is a critical prognostic factor for gastric cancer. Zeb-1 might be a promising therapeutic target.
上皮-间质转化（EMT）被认为在癌症侵袭和转移中发挥重要作用。
在 11 种胃癌细胞系中测量上皮标志物（E-钙黏蛋白）、间充质标志物（波形蛋白）和 Zeb-1 的 mRNA 水平。通过 Zeb-1 敲低进行功能分析。通过计算癌组织中波形蛋白/E-钙黏蛋白 mRNA 表达比，并分析 EMT 状态与临床病理因素、预后的相关性，来确定 116 例胃癌患者的 EMT 状态。
细胞系被分类为上皮或间充质。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、迁移和侵袭的能力。根据 V/E 比（波形蛋白/E-钙黏蛋白比）和 Zeb-1 低或高表达组将患者分类为上皮或间充质。间充质组与弥漫型癌症和 IV 期显著相关。多变量分析显示，EMT 状态（间充质组）是独立的预后因素（P=0.022）。V/E 比与 Zeb-1 表达之间存在显著相关性（r=0.73）。Zeb-1 高组患者的生存明显差于低组（P=0.0071）。
EMT 是胃癌的一个关键预后因素。Zeb-1 可能是一个有前途的治疗靶点。
