ZEB1基因在甲状腺乳头状癌诊断中的意义及对细胞上皮-间质转化的影响

Significance of ZEB1 Gene in Diagnosis and Differentiation of Papillary Thyroid Carcinoma and Its Influence on Cell Epithelial-mesenchymal Transition

目的探讨ZEB1基因在甲状腺乳头状癌诊断中的意义及对细胞上皮-间质转化(EMT)的影响。方法选取90例甲状腺乳头状癌患者作为甲状腺乳头状癌组,另外选取同期进行体检的健康者90例作为正常对照组。实时荧光定量PCR(qPCR)检测2组血清ZEB1基因表达情况,采用受试者工作特征(ROC)曲线分析血清ZEB1基因表达对甲状腺乳头状癌的诊断价值。培养甲状腺乳头状癌细胞TPC-1,作为Con组;将siRNA-Con、siRNA-ZEB1转染进入TPC-1,作为siRNA-Con组和siRNA-ZEB1组。Transwell检测细胞迁移和侵袭;Western blot检测上皮钙黏蛋白(E-cadherin)、神经钙粘蛋白(N-cadherin)、ERK1/2和p-ERK1/2蛋白表达情况。结果与正常对照组相比,甲状腺乳头状癌组ZEB1基因水平表达显著升高(P<0.05)。ZEB1基因表达与临床分期、分化程度、肿瘤大小、淋巴结转移密切相关(P<0.05);ZEB1基因表达与年龄无关(P>0.05)。血清ZEB1基因表达对甲状腺乳头状癌的诊断价值,灵敏度为90.20%,特异度为93.88%,AUC曲线下面积为0.945,P<0.0001。与Con、siRNA-Con组相比,siRNA-ZEB1组ZEB1 mRNA表达水平以及细胞迁移数、细胞侵袭数显著降低(P<0.05)。与Con、siRNA-Con组相比,siRNA-ZEB1组ZEB1 mRNA表达水平以及N-cadherin蛋白表达明显下调(P<0.05),E-cadherin蛋白表达明显上调(P<0.05)。与Con、siRNA-Con组相比,siRNA-ZEB1组ERK1/2蛋白、p-ERK1/2蛋白表达显著降低(P<0.05)。结论ZEB1基因表达对甲状腺乳头状癌具有较高的诊断价值,抑制ZEB1基因能通过MAPK信号通路降低细胞迁移、侵袭能力,抑制上皮间质转化。

Objective To investigate the significance of ZEB1 gene in the diagnosis and differentiation of Papillary thyroid carcinoma and its influence on the cell epithelial-mesenchymal transition(EMT).Methods A total of 90 patients with papillary thyroid carcinoma were selected as the papillary thyroid carcinoma group,and 90 healthy individuals who underwent physical examination were selected as the normal control group.Serum ZEB1 gene expression in the 2 groups was detected by real-time quantitative PCR(qPCR).Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum ZEB1 gene expression in papillary thyroid carcinoma.Papillary thyroid cancer cells TPC-1 were cultured as Con group;siRNA-Con and siRNA-ZEB1 were transfected into TPC-1 as siRNA-Con group and siRNA-ZEB1 group.Transwell detected cell migration and invasion;Western blot detected epithelial cadherin(E-cadherin),neural cadherin(N-cadherin),ERK1/2 and p-ERK1/2 protein expression.Results Compared with the normal control group,the ZEB1 gene expression in the thyroid tumor group was significantly increased(P<0.05).ZEB1 gene expression was closely related to clinical stage,degree of differentiation,tumor size,and lymph node metastasis(P<0.05);ZEB1 gene expression was not related to age(P>0.05).The diagnostic value of serum ZEB1 gene expression for Papillary thyroid carcinoma,the sensitivity was 90.20%,the specificity was 93.88%,the area under the AUC curve was 0.945,P<0.0001.Compared with the Con and siRNA-Con groups,the ZEB1 mRNA expression level,the number of cell migration and the number of cell invasion in the siRNA-ZEB1 group were significantly reduced(P<0.05).Compared with the Con and siRNA-Con groups,the expression of ZEB1 mRNA and the expression of N-cadherin protein in the siRNA-ZEB1 group were significantly reduced(P<0.05),and the expression of E-cadherin protein was significantly increased(P<0.05).Compared with the Con and siRNA-Con groups,the ZEB1 mRNA expression level and the expression of ERK1/2 protein and p-ERK1/2 protein in the siRNA-ZEB1 group were significantly reduced(P<0.05).Conclusion ZEB1 gene expression h-as high diagnostic value for Papillary thyroid carcinoma.Inhibition of ZEB1 gene can reduce cell migration and invasion through MAPK signaling pathway,and inhibit epithelial-mesenchymal transition.