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The present study investigated the clinical significance of Snail, a zinc-finger transcription factor, in the development and progression of gastric cancer. To elucidate the relationship between Snail expression and dedifferentiation status with cancer stem cell phenotype in gastric cancer cells, we used western blot analysis, RT-PCR, quantitative real-time PCR and flow cytometry. Immunohistochemistry staining and evaluation of Snail expression in 10 human normal gastric samples versus 103 clinicopathologically characterized gastric cancer tissues followed by statistical analyses were applied to evaluate the prognostic value of Snail expression for progression and patient survival of gastric carcinomas. The results showed that functional Snail expression interlinks dedifferentiation status with cancer stem cell phenotype in gastric cancer cells. In addition, expression levels of Snail in gastric cancer tissues were significantly associated with tumor cell differentiation, local tumor growth, lymph node status, distant metastasis and tumor stage. The overall survival rate of gastric cancer patients with high Snail expression was significantly lower than for those patients with low Snail expression. Multivariate Cox regression analyses showed that Snail expression is an independent prognostic predictor for patient survival of gastric carcinomas. Thus, our data suggest that Snail expression could be a reliable independent prognostic factor to predict gastric carcinoma progression, which might open a new avenue for potential clinical intervention with functional Snail expression in gastric cancer patients. (Cancer Sci 2012; 103: 1296–1303)