微小RNA-146a和血管内皮生长因子在幽门螺杆菌相关性胃癌组织中的表达情况及临床意义

目的探讨微小RNA(miRNA)-146a和血管内皮生长因子(VEGF)在幽门螺杆菌(Hp)相关性胃癌组织中的表达情况及临床意义。方法收集112例胃癌患者的胃癌组织和癌旁组织标本,所有患者均检测幽门螺杆菌L型(Hp-L)感染情况,采用实时荧光定量聚合酶链反应(qRT-PCR)检测两种组织中miRNA-146a和VEGF mRNA的表达情况,免疫组织化学染色法检测两种组织中VEGF蛋白的表达情况,分析miRNA-146a和VEGF蛋白表达与患者临床特征的关系。采用Pearson相关分析法分析miRNA-146a和VEGF mRNA表达的相关性,受试者工作特征(ROC)曲线分析miRNA-146a对Hp相关性胃癌的诊断价值。结果112例胃癌患者中检测出Hp-L阳性101例。Hp-L阳性和阴性胃癌患者胃癌组织中miRNA-146a的相对表达量均低于相应的癌旁组织,VEGF mRNA的相对表达量均高于相应的癌旁组织,差异均有统计学意义(P﹤0.05)。Hp-L阳性胃癌患者胃癌组织中miRNA-146a的相对表达量低于Hp-L阴性胃癌患者胃癌组织,VEGF mRNA的相对表达量高于Hp-L阴性胃癌患者胃癌组织,差异均有统计学意义(P﹤0.05)。Hp相关性胃癌患者胃癌组织中VEGF蛋白的阳性表达率为89.11%,明显高于癌旁组织的24.75%(P﹤0.01)。TNM分期为Ⅰ~Ⅱ期、无淋巴结转移的Hp相关性胃癌患者胃癌组织中miRNA-146a的高表达率分别高于TNM分期为Ⅲ~Ⅳ期、有淋巴结转移的患者(P﹤0.05),TNM分期为Ⅲ~Ⅳ期、高+中分化的Hp相关性胃癌患者胃癌组织中VEGF蛋白的阳性表达率分别高于TNM分期为Ⅰ~Ⅱ期、低分化的患者(P﹤0.05)。Pearson相关性分析结果显示,Hp相关性胃癌患者胃癌组织中miRNA-146a与VEGF mRNA的表达呈负相关(P﹤0.01)。ROC曲线分析结果显示,miRNA-146a诊断Hp相关性胃癌的临界值为0.56,灵敏度为88.12%,特异度为92.08%,曲线下面积为0.949。结论Hp相关性胃癌患者胃癌组织中miRNA-146a低表达,VEGF高表达,且二者呈负相关,miRNA-146a可作为临床诊断Hp相关性胃癌的重要指标。

Expressions and clinical significance of microRNA-146a and vascular endothelial growth factor in Helicobacter pylori-associated gastric cancer

Objective To investigate the expression and clinical significance of microRNA(miRNA)-146a and vascular endothelial growth factor(VEGF)in Helicobacter pylori(Hp)-associated gastric cancer.Method Gastric cancer tissue and adjacent tissue samples from 112 patients with gastric cancer were collected,Hp-L infection was measured in all patients,quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression of miRNA-146a and VEGF mRNA in all tissues,besides,the expression of VEGF protein in the two types of tissues was detected by immunohistochemistry,and the relationship between miRNA-146a,VEGF protein and clinical characteristics was analyzed.Pearson correlation analysis was employed to analyze the correlation between miRNA-146a and VEGF mRNA,and receiver operating characteristic(ROC)curve was plotted to assess the clinical diagnostic value of miRNA-146a in Hp-associated gastric cancer.Result Among the 112 cases of gastric cancer,101 cases were detected positive for Hp-L.The relative expression of miRNA-146a in gastric cancer tissues with either positive or negative Hp-L was lower than that in adjacent tissues,while the relative expression of VEGF mRNA was higher compared with that in adjacent tissues(P<0.05).The relative expression of miRNA-146a was lower in Hp-L-positive gastric cancer tissues than in Hp-L-negative gastric cancer tissues,and the relative expression of VEGF mRNA was higher in Hp-L-positive gastric cancer tissues(P<0.05).The positive expression rate of VEGF protein in Hp-associated gastric cancer tissues was 89.11%,which was significantly higher than the 24.75%in adjacent tissues(P<0.01).The high expression rate of miRNA-146a in gastric cancer tissues with TNM stageⅠ-Ⅱand no lymph node metastasis was higher than that in those with TNM stageⅢ-Ⅳand lymph node metastasis(P<0.05).The positive expression rate of VEGF protein in Hp-associated gastric cancer tissues with TNM stageⅢ-Ⅳ,high and moderate differentiation was higher than that in those with TNM stageⅠ-Ⅱand low differentiation(P<0.05).Pearson correlation analysis showed that there was a significant negative correlation between miRNA-146a and VEGF mRNA in Hp-associated gastric cancer tissues(P<0.01).ROC analysis revealed that the critical value of miRNA-146a in the diagnosis of Hp-associated gastric cancer was 0.56,with the sensitivity being 88.12%,specificity being 92.08%,and the area under the curve(AUC)was 0.949.Conclusion In Hp-associated gastric cancer tissues,the expression of miRNA-146a is low,while VEGF expression is high,indicating a negative correlation between them.miRNA-146a can be used as a molecular marker for the diagnosis of Hp-associated gastric cancer.