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Epithelial‐to‐mesenchymal transition predicts prognosis in clinical gastric cancer
Author(s) -
Murai Toshifumi,
Yamada Suguru,
Fuchs Bryan C.,
Fujii Tsutomu,
Nakayama Goro,
Sugimoto Hiroyuki,
Koike Masahiko,
Fujiwara Michitaka,
Tanabe Kenneth K.,
Kodera Yasuhiro
Publication year - 2014
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.23564
Subject(s) - vimentin , epithelial–mesenchymal transition , mesenchymal stem cell , cancer , metastasis , cancer research , gene knockdown , medicine , oncology , pathology , cadherin , cell , immunohistochemistry , biology , cell culture , genetics
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 . © 2014 Wiley Periodicals, Inc.