基于TCGA数据库探讨fibronectin 1在甲状腺癌中的表达及临床意义  

Identification of applicable potential value of fibronectin 1 in thyroid cancer in clinic:A study based on TCGA dataset analyses

作　　者：尹璐 杜宁彬[1] 肖迎聪 任建功 Yin Lu;Du Ningbin;Xiao Yingcong;Ren Jiangong(The First Renmin Hospital of Xianyang,Shaanxi Xianyang 712000,China;The Affiliated Hospital of Shaanxi University of Chinese Medicine,Shaanxi Xianyang 712000,China;The Second Hospital of Lanzhou University,Gansu Lanzhou 730000,China)

机构地区：[1]咸阳市第一人民医院,陕西咸阳712000 [2]陕西中医药大学附属医院,陕西咸阳712000 [3]兰州大学第二医院,甘肃兰州730000

出　　处：《现代肿瘤医学》2019年第13期2281-2287,共7页Journal of Modern Oncology

基　　金：咸阳市科学技术研究与发展技术项目(编号:2017K02-96)

摘　　要：目的:研究fibronectin 1(FN1)在甲状腺癌的表达情况,探讨FN1与临床参数的关系,预测其在肿瘤发生发展中的可能机制。方法:从癌症基因组图谱(TCGA)数据库下载甲状腺癌中FN1的RNA SEqV2资料和临床信息,分别采用SPSS进行数据统计比较甲状腺癌组织和非肿瘤甲状腺组织中FN1的表达,利用linkedomics在线分析系统总结fibronectin 1与临床病理参数的关系,使用Kaplan-Meier Plotter进行无复发生存期比较,通过linkedomics在线系统中的基因富集分析(GSEA)分析预测可能相关的信号通路。结果:FN1在甲状腺癌组织中的mRNA表达显著增多(16.663 0±0.378 6 vs 12.182 4±0.139 6,P <0.000 1;16.724 4±0.124 1 vs 12.182 4±0.139 6,P <0.000 1),在乳头状甲状腺癌中的表达偏高( P =0.197×10^-33 ),随T分期增加表达逐渐升高( P =3.321×10^-8 ),在淋巴结转移N 1中表达显著增高( P =9.963×10^-16 ),随病理分级增加表达升高( P =2.780×10^-9 )和随残余增多时表达量升高( P =7.481×10^-3 )。高表达FN1的患者无复发生存期显著短于低表达患者(HR 高表达=2;P HR =0.026<0.05)。FN1高表达样本富集了NF-κB通路,肿瘤坏死因子(TNF)信号通路中激活的PI3K/AKT途径,细胞黏附分子(cell adhesion molecules)中激活的Claudin-1-Notch pathway-EMT途径和甲状腺激素合成(thyroid hormone synthesis)中抑制的PAX8/PPARγ途径等基因集。验证实验结果发现甲状腺癌的肿瘤基质中FN1表达、mRNA转录水平和蛋白表达显著升高。结论:甲状腺癌中FN1上调表达,符合肿瘤研究的相关通路,可以作为预测淋巴结转移和判断预后的重要因子。Objective:To investigate the value of fibronectin 1 in thyroid cancer,the relation between fibronectin 1 and clinic-pathological situation and to prognosticate the mechanisms involved.Methods:The RNA SEqV2 data and clinical information of fibronectin 1 in thyroid cancer from the cancer Genome Atlas (TCGA) was downloaded.The comparisons of fibronectin 1 expression between carcinoma samples and non-cancer tissue were performed statistically by the software SPSS.The relationship between fibronectin 1 and clinic-pathological factors were analyzed by the online tool linkedomics.The gap of the disease free survival was compared by the Kaplan-Meier Plotter.Gene set enrichment analysis (GSEA) was used to predict the gene sets modulated by fibronectin 1.Results:The mRNA expression of fibronectin 1 was significantly high in thyroid cancer[16.663 0±0.378 6 vs 12.182 4±0.139 6( P <0.000 1).16.724 4±0.124 1 vs 12.182 4±0.139 6( P <0.000 1)].High level of fibronectin 1 was showed in papillary thyroid cancer( P =0.197×10^-33 ),advanced T stage( P =3.321×10^-8 ),advanced N 1 stage( P =9.963×10^-16 )advanced cTNM stage( P =2.780×10^-9 ),more residual cancer( P =7.481×10^-3 )and associated with poor disease free survival(HR high expression =2.P HR =0.026<0.05).Fibronectin 1 could regulate the gene sets such as NF-κB pathway,PI3K/AKT pathway in TNF signaling,Claudin-1-Notch pathway-EMT in cell adhesion molecules and PAX8/PPARγ in thyroid hormone synthesis.The proofed experiments showed the mRNA transcription levels and protein expressions increased significantly,which illustrated in the thyroid cancer matrix.Conclusion:Upregulation of fibronectin 1 was found in thyroid cancer,in accordance with the pathways involved and played a potential prognostic marker.

关 键 词：甲状腺癌 fibronectin1 癌症基因组图谱 

分 类 号：R736.1[医药卫生—肿瘤]