BTG4在胃癌中的表达及临床意义

Expression and clinical significance of BTG4 in gastric cancer

目的探讨BTG4在胃癌发生和进展过程中的表达及临床意义。方法利用Oncomine、癌症基因组图谱计划(TCGA)、仙桃数据库和Kaplan-Meier平台分析BTG4 mRNA在胃癌中的表达及其与患者各项临床指标及预后的关系。收集2012年1月至2015年1月锦州医科大学附属第一医院胃腺癌患者癌组织(n=457)及癌旁黏膜组织(n=243,距胃癌组织≥4 cm处获取)石蜡样本。利用实时PCR和Western blotting检测BTG4表达情况,分析BTG4 mRNA表达与患者各项临床指标及预后的关系。将胃腺癌组织及癌旁组织制作成组织芯片,使用免疫组化技术检测各组织芯片中BTG4蛋白表达,分析BTG4蛋白表达与胃腺癌发生、患者临床病理特征及预后的关系。结果与正常黏膜组织比较,胃癌组织中BTG4 mRNA及蛋白表达下调(均P<0.05)。BTG4 mRNA表达与胃癌患者总体生存率和无进展生存率呈负相关(P<0.05)。年龄小、远处转移和BTG4高表达是胃癌患者不良预后的独立危险因素(均P<0.05)。免疫组化结果显示,胃腺癌(59.5%,272/457)和肠化生(20.6%,37/143)组织中BTG4阳性表达高于胃炎(13/100,13%;P<0.05);BTG4阳性表达胃乳头状腺癌高于黏液腺癌(P<0.05),高分化腺癌高于中分化腺癌(P<0.05)。结论BTG4在胃癌组织中低表达,其表达水平与胃癌患者总体生存负相关;BTG4阳性表达与胃癌的发生和发展密切相关。因此,BTG4可作为胃癌预后的预测因子,也可作为胃癌基因治疗的潜在靶标。

Objective To investigate the expression and clinical significance of BTG4 in the occurrence and progression of gastric cancer.Methods Oncomine,The Cancer Genome Atlas Program(TCGA),Xiantao database,and Kaplan-Meier platforms were used to analyze the expression of BTG4 mRNA in gastric cancer and its relationship with various clinical indicators and patient prognoses.Paraffin samples from gastric adenocarcinoma tissues(n=457)and normal mucosal tissues(n=243,≥4 cm from adenocarcinoma tissues)were obtained from the First Affiliated Hospital of Jinzhou Medical University from January 2012 to January 2015.Real-time polymerase chain reaction(PCR)and Western blotting were performed to measure BTG4 expression,and the relationship between BTG4 mRNA expression and various clinical indicators and patient prognoses was analyzed.Gastric adenocarcinoma and para-carcinoma tissues were used for micro assays,and BTG4 protein expression in each micro assay was analyzed using immunohistochemistry.In addition,the relationship between BTG4 protein expression and the occurrence,clinicopathological features,and prognoses of patients with gastric adenocarcinoma was analyzed.Results Compared with normal mucosal tissues,the expression of BTG4 mRNA and protein in gastric cancer tissues was down-regulated(all P<0.05).The expression of BTG4 mRNA was negatively correlated with overall survival and progression-free survival(P<0.05).Young age,distant metastasis,and high expression of BTG4 were independent risk factors for poor prognosis in patients with gastric cancer(P<0.05).Immunohistochemical results showed that BTG4 expression was higher in gastric adenocarcinoma(59.5%,272/457)and intestinal metaplasia(20.6%,37/143)than in gastritis(13/100,13%;P<0.05).BTG4 expression in gastric papillary adenocarcinoma was higher than that in mucinous adenocarcinoma(P<0.05),and BTG4 expression in highly differentiated adenocarcinoma was higher than that in moderately differentiated adenocarcinoma(P<0.05).Conclusion BTG4 expression in gastric cancer tissues was negatively correlated with the overall survival of patients with gastric cancer.Positive expression of BTG4 is closely related to the occurrence and development of gastric cancer.Therefore,BTG4 is a promising predictor of the prognosis of gastric cancer and a potential target for gene therapy in patients with gastric cancer.