激活增强子结合蛋白4在胃癌中的表达及其临床意义

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

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。

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.