Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Cancer Sci. 2012 Jul;103(7):1296-303. doi: 10.1111/j.1349-7006.2012.02295.x. Epub 2012 May 15.
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.
本研究探讨了锌指转录因子 Snail 在胃癌发生和发展中的临床意义。为了阐明 Snail 表达与胃癌细胞去分化状态与癌症干细胞表型之间的关系,我们使用了 Western blot 分析、RT-PCR、实时定量 PCR 和流式细胞术。免疫组织化学染色和对 10 个人类正常胃样本与 103 个临床病理特征明确的胃癌组织中 Snail 表达的评估,并进行了统计学分析,以评估 Snail 表达对胃癌进展和患者生存的预后价值。结果表明,功能性 Snail 表达将去分化状态与胃癌细胞中的癌症干细胞表型联系起来。此外,胃癌组织中 Snail 的表达水平与肿瘤细胞分化、局部肿瘤生长、淋巴结状态、远处转移和肿瘤分期显著相关。高 Snail 表达的胃癌患者的总生存率明显低于低 Snail 表达的患者。多变量 Cox 回归分析表明,Snail 表达是胃癌患者生存的独立预后预测因子。因此,我们的数据表明,Snail 表达可能是预测胃癌进展的可靠独立预后因素,这可能为胃癌患者功能性 Snail 表达的潜在临床干预开辟新途径。