转录抑制因子Snail表达与胃癌Lauren分型的关系研究

Association of transcriptional repressor Snail with Lauren classification of gastric cancer

目的探讨转录抑制因子Snail表达与胃癌Lauren分型的关系。方法Western印迹检测肠型胃癌细胞系（N87）和弥漫型胃癌细胞系（AGS）中Snail和上皮型E钙黏蛋白（E-cadherin）的表达。将糖原合酶激酶．3B（GSK-3B）质粒转染胃癌细胞系，检测Snail和E-cadherin的表达变化。收集2000年2月至2005年12月间在复旦大学附属中山医院行胃癌根治术的77例术后组织标本．采用免疫组织化学染色检测Snail在胃癌组织中表达．并分析其与胃癌Lauren分型之间的关系。结果Snail在N87中低表达，在AGS中高表达；E-cadherin表达与Snail相反。转染GSK-3B后，胃癌细胞Snail表达显著下调，E-cadherin表达显著上调（P〈0．01）。使用不同浓度的GSK-3B抑制剂氯化锂处理后．胃癌细胞Snail表达显著上调，且具有明显浓度依赖性（P〈0．01）。21例肠型胃癌中Snail低表达16例，高表达5例；56例弥漫型胃癌中Snail低表达21例，高表达35例；肠型胃癌中Snail表达明显弱于弥漫型，差异有统计学意义（P〈0．01）。结论Snail的表达与胃癌Lauren分型有关．是一种潜在的确定胃癌分型的分子标志物。

Objective To explore the association of Snail expression and Lauren classification of gastric cancer. Methods The protein levels of Snail and E-cadherin were detected by Western blot in N87（intestinal-type gastric cancer cell line） and AGS（diffuse-type gastric cancer cell line） cell lines and those after transfection of GSK-3β plasmid. The study included a total of 77 patients with primary gastric cancer who underwent curative gastrectomy in the Zhongshan Hospital from February 2000 to December 2005 without any chemotherapy or radiation therapy before surgery. Tissues of gastric cancer specimens were stained using immunohistochemistry to determine Snail expression. Results Snail expression was low in N78 and high in AGS. E-cadherin expression showed reverse expression pattern. After transfeetion with GSK-3β, the expression of Snail was significantly suppressed and that of E-cadherin elevated （P〈0.01）. Different concentrations of GSK-3β inhibitor lithion chloride were used to treat the cell lines and Snail expression was significantly up-regulated in a dose-dependent manner （P〈0.01）. Snail expression was elevated in 16 out of 21 N78 cell lines, and in 21 out of 56 AGS cell lines, and the difference was statistically significant （P〈0.01）. Conclusion The expression of Snail is closely associated with the Lauren classification of gastric cancer, and it may be a potential marker of the gastric cancer classification.