Epithelial-to-mesenchymal transition predicts prognosis in clinical gastric cancer.
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.
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Toshifumi
T
Murai
Suguru
S
Yamada
Bryan C
BC
Fuchs
Tsutomu
T
Fujii
Goro
G
Nakayama
Hiroyuki
H
Sugimoto
Masahiko
M
Koike
Michitaka
M
Fujiwara
Kenneth K
KK
Tanabe
Yasuhiro
Y
Kodera
D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000401:mortality / Q000473:pathology*; D014157:Transcription Factors / Q000032:analysis; D000071799:Zinc Finger E-box-Binding Homeobox 1
D018398:Homeodomain Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
Zeb-1; epithelial-to-mesenchymal transition; gastric cancer; prognosis