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Open Access Highly Accessed Research article

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

Na Ri Shin14, Eun Hui Jeong5, Chang In Choi34, Hyun Jung Moon14, Chae Hwa Kwon14, In Sun Chu6, Gwang Ha Kim24, Tae Yong Jeon34, Dae Hwan Kim34, Jae Hyuk Lee5 and Do Youn Park14*

Author affiliations

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

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Citation and License

BMC Cancer 2012, 12:521  doi:10.1186/1471-2407-12-521

Published: 14 November 2012

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.

Conclusion

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

Keywords:
Stomach; Adenocarcinoma; Snail; Lymph node metastasis; Survival