甲状腺乳头状癌颈部淋巴结转移相关基因的生物信息学分析

Bioinformatics analysis for genes related to cervical lymph node metastasis of papillary thyroid carcinoma

目的:利用生物信息学方法分析甲状腺乳头状癌(papi l lar y thyroid carcinoma,PTC)颈部淋巴结转移的关键基因。方法:从美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)公共数据平台高通量基因表达(Gene Expression Omnibus,GEO)数据库检索得到PTC的基因芯片GSE60542,使用GEO2R在线分析工具分别筛选PTC和癌旁组织的差异表达基因(差异表达基因集A)以及PTC与颈部淋巴结转移癌组织之间的差异表达基因(差异表达基因集B)。进一步筛选出差异表达基因集A和差异表达基因集B交集的差异表达基因集C。通过生物信息学工具David,String,cBioPortal对差异表达基因集C进行生物学功能及其编码蛋白的互作分析,并对差异表达基因集C进行生存分析。结果:通过分析GSE60542芯片数据,一共获得1086个差异表达基因A、194个差异表达基因B、39个差异表达基因C。基因本体(Gene Ontology,GO)分析显示:差异表达基因集C主要的分子功能与氧化还原酶活性、蛋白质同源二聚化活性、生长因子结合有关;这些基因主要参与细胞增殖、甲状腺激素的产生、神经细胞凋亡过程的负调节、γ-氨基丁酸信号转导途径等生物学过程。通过cBioPortal在线分析网站,初步筛选出对患者生存时间影响较大的基因CCL21。结论:基因芯片结合生物信息学方法能够有效分析PTC组织、癌旁组织以及颈部淋巴结转移癌组织间差异表达基因,并筛选出PTC颈部淋巴结转移相关的关键基因,为进一步研究PTC颈部淋巴结转移的分子机制提供一定的指导。

Objective:Bioinformatics methods were used to analyze key genes in cervical lymph node metastasis of papillary thyroid carcinoma(PTC).Methods:Microarray data of PTC GSE60542 was searched from Gene Expression Omnibus(GEO)database of National Center for Biotechnology Information(NCBI).The GEO2R online analysis tool was used to screen differentially expressed genes between PTC and paracarcinoma tissues(differentially expressed gene set A)and differentially expressed genes between PTC and cervical metastatic lymph nodes(differentially expressed gene set B).The differentially expressed gene set C of the intersection of differentially expressed gene set A and differentially expressed gene set B was further screened.And bioinformatics tools including David,String and cBioPortal were applied to analyze the biological function of differentially expressed gene set C and their encoded proteins interaction.Then,we performed survival analysis on key genes.Results:By analyzing the GSE60542 microarray data,a total of 1086 differentially expressed gene A,194 differentially expressed gene B,and 39 differentially expressed gene C were obtained.GO analysis showed that these genes are mainly involved in the molecular function of oxidoreductase activity,protein homodimerization activity,growth factor binding and involved in the biological processes of cell proliferation,thyroid hormone generation,negative regulation of neuron apoptotic process,gamma-aminobutyric acid signaling pathway.Through the online cBioPortal analysis website,the gene CCL21,which had a great influence on the survival time of patients,was initially screened.Conclusion:Microarray combined with bioinformatics methods can effectively analyze the differentially expressed genes between PTC tissues,paracarcinoma tissues,and cervical metastatic lymph node tissues,which may provide guidance for molecular mechanisms research of PTC pathogenesis.