Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer
- Equal contributors
1 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
2 Department of Internal Medicine, Pusan National University Hospital and Pusan National University School of Medicine, Busan, South Korea
3 Department of Surgery, Pusan National University Hospital and Pusan National University School of Medicine, Busan, South Korea
4 BioMedical Research Institute, Pusan National University Hospital, Busan, South Korea
5 Department of Pathology, Cheonam National University, Gwangju, South Korea
6 Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea
BMC Cancer 2012, 12:521 doi:10.1186/1471-2407-12-521Published: 14 November 2012
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.