甲状腺乳头状癌脑转移差异表达基因生物学功能分析及关键调控基因筛选

Biological function analysis of differentially expressed genes in brain metastasis of papillary thyroid carcinoma and screening of hub genes

目的采用生物信息学方法分析甲状腺乳头状癌(PTC)脑转移差异表达基因的生物学功能,并筛选PTC脑转移的关键调控基因。方法从GEO数据库获取基因芯片GSE66463,利用GEO2R中GEOquery、limma包筛选PTC脑转移灶癌组织差异表达基因,对差异表达基因进行基因本体论(Gene Ontology,GO)功能注释,利用京都基因和基因组数据库对差异表达基因的信号通路进行富集分析。通过String数据库构建差异表达基因的蛋白互作网络,筛选可能参与PTC脑转移的关键调控基因,分别基于GEPIA数据库、人类蛋白质表达图谱数据库数据分析PTC脑转移关键调控基因及蛋白与PTC患者预后的关系。结果PTC脑转移灶癌组织中共183个差异表达基因,其中表达上调82个、下调101个。PTC脑转移灶癌组织差异表达基因生物学功能主要有金属离子动态平衡、小分子转运及分子细胞间黏附等,信号通路主要集中在风湿性炎症信号通路、NF-kB信号通路及IL17信号通路等。β-1,3-N-乙酰氨基葡萄糖氨基转移酶(B3GNT7)、丝氨酸/苏氨酸激酶(BUB1)、细胞分裂周期蛋白20(CDC20)、集落刺激因子2(CSF2)、趋化因子CXC配体2、白细胞介素1α(IL1α)、IL1β、骨诱导因子、骨调蛋白、脯氨酸/精氨酸丰富端亮氨酸丰富重复蛋白可能是参与PTC脑转移的关键调控基因。与B3GNT7低表达者比较,B3GNT7基因及蛋白高表达的PTC患者预后较好(P均<0.05)。结论PTC脑转移的差异表达基因的生物学功能主要有金属离子动态平衡、小分子转运及分子细胞间黏附等。PTC脑转移的关键调控基因主要有B3GNT7、BUB1及CDC20等。

Objective To analyze the differentially expressed genes of brain metastasis in papillary thyroid carcinoma(PTC)and to screen the hub genes by bioinformatics.Methods Gene chip GSE66463 was retrieved from Gene Expression Omnibus(GEO)database,and the differentially expressed genes of brain metastasis in PTC were screened by GEO2R invoking GEOquery and Limma packages.The functional annotations of differentially expressed genes were conducted by Gene Ontology(GO).Meanwhile,the enrichment analysis of signal pathways of differentially expressed genes was explored by Kyoto Encyclopedia of Genes and Genomes(KEGG).The protein-protein interaction network was structured by String database to screen the hub genes that might participate in brain metastasis of PTC.The correlation between hub gene and prognosis of PTC was respectively studied by Gene Expression Profiling And Interactive Analyses(GEPIA)and The Human Protein Atlas(HPA)databases.Results A total of 183 differentially expressed genes was screened out,of which,82 genes were up-regulated and 101 genes were down-regulated.Functional analysis showed that the differentially expressed genes were related to metal ion dynamic balance,small molecule transport,and molecular intercellular adhesion.Signal pathways were mainly enriched in rheumatoid arthritis,NF-ΚB,IL-17 and other signaling pathway.B3GNT7,BUB1,CDC20,CSF2,CXCL2,IL1A,IL1B,OGN,OMD,and PRELP were the hub genes of brain metastasis in PTC.Compared with patients with low expression of B3GNT7,PTC patients with high expression of B3GNT7 gene and protein had a better prognosis(P<0.05).Conclusions Differentially expressed genes in brain metastasis of PTC are related to metal ion dynamic balance,small molecule transport,and molecular intercellular adhesion.B3GNT7,BUB1,CDC20 and some other genes may be the hub genes of brain metastasis in PTC.