上皮细胞-间质细胞转化相关基因FN1在甲状腺癌的表达及对预后的预测意义

Expression of EMT-related gene FN1 in thyroid carcinoma and its predictive significance for prognosis

目的探究上皮细胞-间质细胞转化(EMT)对甲状腺癌发生的潜在机制,了解EMT相关基因在甲状腺癌组织表达情况并探讨其预后指导价值。方法从TCGA数据库下载568份甲状腺癌转录组表达谱数据及508例患者临床资料,寻找转录组表达谱差异基因,并对差异基因进行功能富集分析。Western blot分别检测华北理工大学附属医院5例患者手术切除的甲状腺癌组织和相应癌旁组织纤维连接蛋白1(FN1)表达情况,以验证FN1差异表达;并检测上皮标志物E-cadherin表达水平,以了解甲状腺癌组织EMT水平。分析EMT相关基因FN1、MMP11和GLT8D2与差异基因相关性,并利用EMT相关基因构建Cox回归模型,预测Ⅰ~ⅣC期甲状腺癌患者的预后。结果差异基因分析结果显示共1136个基因在肿瘤和正常组织中差异表达,这些基因11.6%富集于EMT通路;Western blot检测FN1和E-cadherin结果显示,在甲状腺癌组织中FN1高表达,E-cadherin低表达;相关性分析结果显示,FN1、MMP11和GLT8D2与1136个差异基因有较高相关性,尤其是FN1与484个基因皮尔森相关系数绝对值>0.5,最强正相关系数为0.853,最强负相关系数为-0.819;Cox回归分析结果显示,FN1、MMP11和GLT8D2联合对Ⅰ~ⅣC期患者预后有较高预测价值(AUC=0.893)。结论甲状腺癌组织存在EMT,FN1基因可能是甲状腺癌机制研究的重要分子。

Objective To investigate the potential mechanism of epithelial-mesenchymal transition(EMT) on the occurrence of thyroid cancer,to understand the expression of EMT-related genes in thyroid cancer tissues,and to explore its prognostic value.Methods A total of 568 transcriptome expression profile data of thyroid cancer and 508 patients′ clinical data were download from the TCGA database to find differential genes in the transcriptome group expression profile,and to analyze the functional enrichment of differential genes.Western blot was used to detect FN1 in thyroid cancer tissues and corresponding adjacent tissues from 5 patients to verify the differential expression of FN1.The expression level of epithelial marker E-cadherin was detected to understand the level of EMT in thyroid cancer tissues.The correlation between EMT-related genes FN1,MMP11,GLT8 D2 and differential genes were analyzed,and a Cox model was constructed using EMT-related genes to predict the prognosis of patients with stage Ⅰ to ⅣC thyroid cancer.Results Differential gene analysis showed that a total of 1 136 genes were differentially expressed in tumors and normal tissues.These genes were 11.6% enriched in the EMT pathway;Western blot showed that FN1 was highly expressed and E-cadherin was lowly expressed in thyroid cancer tissues.Correlation analysis showed that FN1,MMP11,GLT8 D2 were highly correlated with 1 136 differential genes,in particular,the absolute value of the Pearson correlation coefficient of FN1 and 484 genes was greater than 0.5,the strongest positive correlation coefficient was 0.853,and the strongest negative correlation coefficient was-0.819.The results of Cox regression analysis showed that the combination of FN1,MMP11 and GLT8 D2 had a higher prognostic value for patients with stage Ⅰ~ⅣC(AUC=0.893).Conclusions EMT exists in thyroid cancer tissues,and FN1 gene may be an important molecule in the study of mechanism of thyroid cancer.