Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer

• Published in: BMC cancer Vol. 12; no. 1; p. 521
• Main Authors: Shin, Na Ri, Jeong, Eun Hui, Choi, Chang In, Moon, Hyun Jung, Kwon, Chae Hwa, Chu, In Sun, Kim, Gwang Ha, Jeon, Tae Yong, Kim, Dae Hwan, Lee, Jae Hyuk, Park, Do Youn
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.11.2012; BioMed Central; BMC
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - secondary; Adult; Aged; Aged, 80 and over; Analysis; Biomedical research; Blotting, Western; Cancer; Cancer patients; Cell adhesion & migration; Cell Line, Tumor; Cell Movement; Chemotherapy; Development and progression; DNA microarrays; Female; Gastric cancer; Gene expression; Genes; Genetic aspects; Humans; Liver cancer; Lymph node metastasis; Lymphatic metastasis; Lymphatic Metastasis - genetics; Lymphatic Metastasis - pathology; Male; Matrix Metalloproteinase 11 - metabolism; Medicine; Membrane filters; Metastasis; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Proteins - metabolism; Physiological aspects; Prognosis; Proteins; Real-Time Polymerase Chain Reaction; RNA, Small Interfering; Snail; Snail Family Transcription Factors; Stem cells; Stomach; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Studies; Survival; Thermal cycling; Tissue Array Analysis; Transcription Factors - metabolism; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Zinc finger proteins
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-12-521

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. 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. 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. Snail significantly affects invasiveness/migratory ability of GCs, and may also be used as a predictive biomarker for prognosis or aggressiveness of GCs.