FAT4、CUL4、YAP 在胃癌组织中的 表达及其临床意义

Expressions of FAT4, CUL4 and YAP in gastric cancer and their clinical significance

摘要:

目的 探讨胃癌细胞侵袭过程中FAT4、CUL4、YAP 在调控Hippo 通路的作用及机制。方法 免 疫组织化学法检测胃癌组织及正常胃组织中FAT4、CUL4 及YAP 的表达情况，分析其表达水平与胃癌患者临 床病理特征的关系；Western blot 法测定胃癌组织及正常胃组织中FAT4、CUL4 及YAP 蛋白表达情况。结果 胃 癌细胞中FAT4、CUL4 和YAP 在性别、病理类型阳性表达率比较，差异无统计学意义（P >0.05），在胃癌的 分化程度及淋巴结转移之间比较，差异有统计学意义（P <0.05），且淋巴结无转移、分化程度较高的FAT4、 CUL4 和YAP 阳性表达率高；免疫组织化学发现胃癌组织中CUL4 和YAP 表达量较正常胃组织增多，胃癌 组织中FAT4 表达量较正常胃组织减少；胃癌组织中CUL4 及YAP 蛋白表达量高于正常胃组织，差异有统 计学意义（P <0.05）；胃癌组织中FAT4 蛋白表达量低于正常胃组织，差异有统计学意义（P <0.05）。结论 FAT4 通过调控Hippo-YAP 信号通路抑制胃癌细胞侵袭过程，CUL4 通过调控Hippo-YAP 信号通路促进胃 癌细胞侵袭过程。

Abstract:

Objective To investigate the role and mechanism of FAT4, CUL4 and YAP in involvement of Hippo pathway in invasion of gastric cancer cells. Methods Immunohistochemistry was used to detect the expressions of FAT4, CUL4 and YAP in gastric cancer tissues and normal gastric tissues, and their relationships with clinicopathological characteristics of the patients with gastric cancer were analyzed. Western blot assay was used to detect the protein expressions of FAT4, CUL4 and YAP in the gastric cancer tissues and the normal gastric tissues. Results There was no significant difference in the positive expression rate of FAT4, CUL4 or YAP between the gastric cancer patients with different sexes and different pathological types (P > 0.05). There were statistically significant differences in the positive expression rates of FAT4, CUL4 and YAP between the gastric cancer patients with different degree of tumor differentiation and between the patients with and without lymph node metastasis (P < 0.05), the positive expression rates of FAT4, CUL4 and YAP were higher in the patients with higher degree of differentiation and without lymph node metastasis. The expressions of CUL4 and YAP in the gastric cancer tissues increased compared with the normal gastric tissues (P < 0.05), while the expression of FAT4 in the gastric cancer tissues was lower than that in the normal gastric tissues (P < 0.05). Conclusions FAT4 inhibits the invasion of gastric cancer cells through regulation of Hippo-YAP signaling pathway. CUL4 promotes gastric cancer cell invasion through regulating Hippo-YAP signaling pathway.