摘要
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。
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.
作者
许丽芳
任鸿昌
黄志君
闫虹
XU Lifang;REN Hongchang;HUANG Zhijun;YAN Hong(Department of Outpatient,Chinese People’s Liberation Army Strategic Support Force Characteristic Medical Center,Beijing 100101,China;Department of General Surgery,Chinese People’s Liberation Army Strategic Support Force Characteristic Medical Center,Beijing 100101,China)
出处
《癌症进展》
2020年第7期739-743,共5页
Oncology Progress
