激活增强子结合蛋白4在胃癌中的表达及其临床意义

目的:探讨激活增强子结合蛋白4（activating enhancer binding protein 4，AP4）在胃癌组织中的表达及其与临床病理特征的关系。方法:采用RT-PCR和Western blot检测胃癌细胞株BGC823和正常胃上皮细胞中AP4 mRNA和蛋白的表达；应用RT-PCR及免疫组化法检测90例胃癌组织中AP4 mRNA和蛋白的表达；进一步采用Log-rank检验和Cox回归模型对结直肠癌患者的预后因素进行分析，并用Kaplan-Meier计算不同AP4表达情况患者的生存率曲线。结果:与正常胃上皮细胞相比，胃癌细胞株BGC823中AP4 mRNA和蛋白的表达水平均显著升高（均P＜0.05）；在胃癌组织中，AP4 mRNA的表达水平也明显高于配对的癌旁组织（3.848±0.426 vs 1.411±0.405，P＜0.05）；在蛋白水平，胃癌组织也显著高于配对的癌旁组织，且AP4蛋白表达与胃癌的脉管浸润（P＜0.05）、浸润深度（P＜0.05）及TNM分期（P＜0.05）相关，而与患者的性别、年龄、分化程度、肿瘤位置、淋巴结转移和远处转移无关（均P＞0.05）；Kaplan-Meier 单因素回归分析显示，AP4蛋白是影响胃癌患者预后的重要因素（P＜0.05），进一步Cox多因素回归分析显示AP4蛋白是胃癌患者的独立预后因素（P＜0.05）。结论:AP4高表达与胃癌的发生、发展、转移及预后关系密切，可能成为协助胃癌诊断和治疗的新的生物标志物。

The significance of activating enhancer binding protein 4 expression in gastric cancer

Objective:To investigate the expression and correlation with clinicopathological parameters of activating enhancer binding protein 4 （AP4） in gastric cancer.Methods:AP4 expression in BGC823 and normal gastric cells was detected by RT-PCR and Western blot.The mRNA and protein expression of AP4 in 90 gastric cancer tissues and paired adjacent tissues of 90 cases were investigated by RT-PCR and immunohistochemical SP method.Kaplan-Meier survival curves，Log-rank test and Cox multivariate test regression were used to analyze the clinicopathological prognostic factors of gastric cancer.Results:The mRNA and protein expression of AP4 in gastric cancer cell line (BGC823) was higher than normal gastric cells (P<0.05，respectively).AP4 was highly expressed at mRNA levels in the gastric tissue samples compared with the paired adjacent normal tissues (3.848±0.426 vs 1.411±0.405，P<0.05).Furthermore，compared to paired adjacent tissue，AP4 protein was highly expressed in gastric cancer tissue and the expression level of AP4 protein was significantly associated with vascular invasion (P＜0.05)，depth of invasion (P＜0.05) and TNM stage (P＜0.05)，but not to gender，age，differential degree，tumor site，lymph node metastasis and distant metastasis (P＞0.05，respectively).Kaplan-Meier univariate analysis showed that AP4 protein was an important factor for affecting the prognosis of gastric cancer (P＜0.05)，and further Cox regression analysis demonstrated that AP4 protein was an independent prognostic risk factor of gastric cancer (P＜0.05).Conclusion:The high expression of AP4 is closely related to the occurrence，development，metastasis and prognosis of gastric cancer，and it may become a new biomarker to assist in the diagnosis and treatment of gastric cancer.