title: Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer.
abstract: BACKGROUND
  Epithelial-mesenchymal transition (EMT) plays a significant role in tumor progression and invasion. Snail is a known regulator of EMT in various malignant tumors. This study investigated the role of Snail in gastric cancer.
  
  
  METHODS
  We examined the effects of silenced or overexpressed Snail using lenti-viral constructs in gastric cancer cells. Immunohistochemical analysis of tissue microarrays from 314 patients with gastric adenocarcinoma (GC) was used to determine Snail's clinicopathological and prognostic significance. Differential gene expression in 45 GC specimens with Snail overexpression was investigated using cDNA microarray analysis.
  
  
  RESULTS
  Silencing of Snail by shRNA decreased invasion and migration in GC cell lines. Conversely, Snail overexpression increased invasion and migration of gastric cancer cells, in line with increased VEGF and MMP11. Snail overexpression (≥75% positive nuclear staining) was also significantly associated with tumor progression (P < 0.001), lymph node metastases (P = 0.002), lymphovascular invasion (P = 0.002), and perineural invasion (P = 0.002) in the 314 GC patients, and with shorter survival (P = 0.023). cDNA microarray analysis revealed 213 differentially expressed genes in GC tissues with Snail overexpression, including genes related to metastasis and invasion.
  
  
  CONCLUSIONS
  Snail significantly affects invasiveness/migratory ability of GCs, and may also be used as a predictive biomarker for prognosis or aggressiveness of GCs.
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, 1-10 Ami-Dong, Seo-Gu, Busan, 602-739, South Korea.
authors.forename: Na Ri
authors.initials: NR
authors.lastname: Shin
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Jeong
authors.forename: Chang In
authors.initials: CI
authors.lastname: Choi
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Moon
authors.forename: Chae Hwa
authors.initials: CH
authors.lastname: Kwon
authors.forename: In Sun
authors.initials: IS
authors.lastname: Chu
authors.forename: Gwang Ha
authors.initials: GH
authors.lastname: Kim
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Jeon
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Do Youn
authors.initials: DY
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D053507:Matrix Metalloproteinase 11 / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C511771:MMP11 protein, human; D053507:Matrix Metalloproteinase 11