刘蕾 李砚 郭元彪

[摘要] 目的 研究SALL4在胃癌患者与健康人群血清中含量差异，并探讨SALL4分子在胃癌进展中的作用。 方法 选择2016年3月～2018年4月在成都市第三人民医院治疗的47例胃癌患者和参加体检的29例健康志愿者。采用酶联免疫吸附测定方法检测血清中SALL4含量；采用Real-time PCR和Western blot分析SALL4在多种胃癌细胞株和胃黏膜细胞株中的mRNA水平和蛋白水平表达情况；通过siRNA干扰研究SALL4对胃癌细胞迁移和侵袭能力的影响；Western blot分析上皮间质转化（EMT）相关分子表达情况。 结果 SALL4在胃癌患者血清中的含量显著高于健康志愿者，差异有高度统计学意义（P < 0.0001）。SALL4在多种胃癌细胞株中mRNA水平和蛋白水平的表达情况均高于胃黏膜细胞株。干扰SALL4表达后，胃癌细胞的迁移能力和侵袭能力均显著降低，差异有统计学意义（P < 0.05）。SALL4表达降低可导致E-cadherin表达上调，snail、β-catenin和Wnt3a表达下调。 结论 SALL4与胃癌进展相关，可能通过诱导胃癌细胞EMT进程，促进细胞迁移和侵袭。

[关键词] SALL4；胃癌；细胞迁移；上皮间质转化

[中图分类号] R735.2；R73-37 [文献标识码] A [文章编号] 1673-7210（2018）10（b）-0009-05

[Abstract] Objective To investigate the difference of serum SALL4 levels between gastric cancer patients and healthy people， and to explore the role of SALL4 in the progression of gastric cancer. Methods A total of 47 patients with gastric cancer who were treated in the Third People′s Hospital of Chengdu from March 2016 to April 2018 and 29 healthy volunteers who participated in the physical examination were selected. The serum levels of SALL4 were detected by ELISA. The expression of SALL4 in mRNA level and protein level in various gastric cancer cell lines and gastric mucosa cells were analyzed by Real-time PCR and Western blot respectively. The effects of SALL4 on the cell migration and invasion ability were analyzed by siRNA interference. The expression levels of related molecules of epithelial-mesenchymal transition （EMT） were detected by Western blot. Results The serum SALL4 levels in patients with gastric cancer were significantly higher than those in healthy volunteers， and the difference was highly statistically significant （P < 0.0001）. The expression of SALL4 mRNA and protein in various gastric cancer cell lines was higher than that in gastric mucosal cell lines. The migration and invasion ability of gastric cancer cells were significantly decreased after interfering SALL4 expression， and the differences were statistically significant （P < 0.05）. Decreased expression of SALL4 leaded to the up-regulation of E-cadherin expression and the down-regulation of snail， β-catenin and Wnt3a. Conclusion SALL4 is related to the progression of gastric cancer. It may promote cell migration and invasion by inducing the EMT process in gastric cancer cells.

[Key words] SALL4； Gastric cancer； Cell migration； Epithelial-mesenchymal transition

胃癌是全球最常見的四大恶性肿瘤之一，超过50%的病例发生在亚洲东部。在亚洲，胃癌是继乳腺癌和肺癌后最常见的第三大恶性肿瘤，是继肺癌后第二常见的癌症死亡原因[1]。虽然近年来肿瘤综合治疗技术快速发展，但胃癌患者整体临床疗效并没有显著改善。淋巴结转移被认为是胃癌预后的关键指标[2]。探索胃癌转移的分子机制有望为胃癌临床治疗提供新的思路。人类婆罗双树样基因-4（sal-like protein 4，SALL4）是一种锌指蛋白转录因子，位于人类20号染色体q13，有4个外显子[3]。SALL4不仅在早期胚胎发育、维持胚胎干细胞多能性和自我更新方面发挥着重要的作用，而且与遗传性疾病、血液系统肿瘤、生殖细胞肿瘤等多种恶性肿瘤密切相关[4]。本研究通过检测SALL4在健康人群和胃癌患者血清中的水平，分析SALL4对胃癌细胞迁移能力的影响及相关分子机制，探索SALL4分子在胃癌发生与转移中的作用。……