甲状腺乳头状癌预后不良相关基因的生物信息学分析  

Bioinformatics analysis of genes associated with poor prognosis in papillary thyroid carcinoma

作　　者：高建 张国烈[1] 林元美[1] 章国亮 陈一钧 GAO Jian;ZHANG Guolie;LIN Yuanmei;ZHANG Guoliang;CHEN Yijun(The First Department of Thyroid Surgery,Affiliated Hospital of Putian University,Putian 351100,Fujian,China)

机构地区：[1]莆田学院附属医院甲状腺外一科,福建莆田351100

出　　处：《右江医学》2020年第7期492-500,共9页Chinese Youjiang Medical Journal

基　　金：福建省教育厅中青年教师教育科研项目(JAT190558)。

摘　　要：目的通过甲状腺乳头状癌(papillary thyroid carcinoma,PTC)生物信息学分析,获取与PTC预后显著相关的基因,为PTC的发病机制提供理论依据。方法从NCBI的GEO Databases数据库检索PTC的芯片数据GSE3678、GSE33630和GSE82208,三组基因芯片共包含94例PTC及77例癌旁组织基因表达谱。使用GEO2R工具分析PTC与癌旁组织差异表达的基因;将共表达的基因导入可视化数据库(the database for annotation,visualization and integrated discovery,DAVID)进行基因富集分析(gene ontology,GO)和信号通路分析(kyoto encyclopedia of genes and genomes,KEGG);使用STRING和Cytoscape进行蛋白质互作网络分析(protein-protein interaction,PPI);使用GEPIA分析核心基因的生存信息。随后培养PTC细胞株,收集52例临床组织样本,分别验证FN1在PTC组织样本和细胞中的表达情况。结果 GSE3678、GSE33630和GSE82208共有152个共表达基因,其中24个上调表达,128个下调表达。这152个异常表达基因(different expression genes,DEGs)在PTC细胞组分、分子功能、生物学行为上主要集中于影响细胞正常分化及富集于甲状腺激素合成信号通路等。PPI显示,基因AGTR1、AVPR1A、EGR2、FGFR2、FN1、FOSB、GNA14、JUN、EDN、IRS1、SPP1相互之间紧密相关。进一步的生存分析显示,AGTR1、AVPR1A、EGR2、FGFR2、FN1、FOSB、GNA14、JUN与无病生存时间相关,但总体生存时间无差异。FN1在31例(59.61%)PTC组织中呈上调表达,平均表达倍数变化为(3.75±5.90)倍。与Nthy-ori 3-1细胞相比,BCPAP和TPC-1中FN1的表达水平分别提高了(4.75±1.12)倍、(11.89±3.53)倍(P<0.01)。结论 AGTR1、AVPR1A、EGR2、FGFR2、FN1、FOSB、GNA14、JUN在PTC中异常表达且预示着较差的临床预后;FN1基因在PTC组织和细胞株中表达增高。Objective To obtain genes significantly associated with papillary thyroid carcinoma(PTC) by bioinformatics analysis of PTC,so as to provide theoretical basis for the pathogenesis of PTC.Methods The data of PTC chip(GSE3678,GSE33630 and GSE82208) were retrieved from the GEO databases of NCBI.The gene expression profiles of 94 PTCs and 77 paracancerous tissues were included in the three gene chips.GEO2 R tool was used to analyze genes differentially expressed in PTC and adjacent tissues.The co-expressed genes were introduced into the visual database(the database for annotation,visualization and integrated discovery,DAVID) for gene enrichment analysis(gene ontology,GO) and signal pathway analysis(kyoto encyclopedia of genes and genomes,KEGG).The network analysis of protein-protein interaction(PPI) was performed by STRING and Cytoscape.GEPIA was used to analyze survival information of core genes.PTC cell lines were cultured and 52 clinical tissue samples were collected,and the expressions of FN1 in PTC tissue samples and cells were verified,respectively.Results There were 152 co-expressed genes in GSE3678,GSE33630 and GSE82208,of which 24 were up-regulated and 128 were down-regulated.In PTC cell components, molecular functions and biological behavior,these 152 abnormal expression genes(DEGs) mainly focused on affecting the normal differentiation of PTC cells and enriching in the signal pathway of thyroid hormone synthesis.PPI showed that AGTR1,AVPR1 A,EGR2,FGFR2,FN1,FOSB,GNA14,JUN,EDN,IRS1 and SPP1 were closely related to each other.Further survival analysis showed that AGTR1,AVPR1 A,EGR2,FGFR2,FN1,FOSB,GNA14 and JUN were related to disease-free survival time,but there was no difference in overall survival time.FN1 was up-regulated in PTC tissues of 31 cases(59.61%),and the average expression multiple was(3.75±5.90) times.Compared with Nthy-ori 3-1 cells,the expression levels of FN1 in BCPA and TPC-1 increased by(4.75±1.12) times and(11.89±3.53) times,respectively(P<0.01).Conclusion AGTR1,AVPR1 A,EGR2,FGFR2,FN1,FO

关 键 词：甲状腺乳头状癌 生物信息学 异常表达基因 FN1 临床预后 

分 类 号：R736.1[医药卫生—肿瘤]