目的 利用生物信息学分析挖掘环境内分泌干扰物(environmental endocrine disruptors,EDCs)对甲状腺癌(thyroid cancer,TC)的作用.方法 应用毒物基因组学数据库(comparative toxicogenomic database,CTD)检索双酚A(bisphenol A,BPA)、四氯二苯并对二噁英(tetrachlorodibenzo-p-dioxin,TCDD)和邻苯二甲酸二酯[di-(2-ethylhcxyl)phthalate,DEHP],确定其与TC发病的相关基因;通过venn图获取交集基因,并对上述交集基因进行基因功能注释(gene ontology,Go)分析和京都基因与基因组百科全书(encyclopedia of genes and genome,KEGG)通路分析;构建蛋白质互作网络(protein-protein interaction,PPI)并筛选关键基因.结果 识别3种EDCs对TC影响的15个交集基因.这些基因在GO分析中主要富集于基因表达、转录调控等生理过程;在KEGG分析中主要富集于癌症通路、脂质和动脉粥样硬化通路和甲状腺肿瘤通路.通过PPI网络筛选出原癌基因(HRAS)、肿瘤抑制基因(TP53)、白介素6(IL-6)、肿瘤坏死因子(TNF)、前列腺素内过氧化物合酶(PTGS2)和过氧化物酶体增殖物激活受体γ(PPARG)6种关键基因.结论 HRAS、TP53、IL6、TNF、PTGS2和PPARG可能是3种EDCs作用的重要靶点,提示基因突变、免疫炎症反应激活和脂质代谢异常在TC发生、发展中发挥一定的重要作用.
The impact of environmental endocrine disruptors on thyroid cancer:a bioinformatic analysis
Objective To explore the impact of environmental endocrine disruptors(EDCs)on thyroid cancer(TC)using bioinformatics analysis.Methods We searched bisphenol A(BPA),tetrachlorodibenzo-p-dioxin(TCDD)and di-(2-ethylhcxyl)phthalate(DEHP)through the comparative toxicogenomic database(CTD)to determine genes related to TC pathogenesis.Gene ontology(GO)functional annotation and Kyoto Encyclopedia of genes and Genome(KEGG)analysis were carried out to preliminarily establish genetic regulation network model of these co-occurred genes generated by Venn diagram.Moreover,protein-protein interaction(PPI)network was constructed to identify key genes.Results There were 15 genes co-occurred in the impact of BPA,TCDD,or DEHP on TC.These related genes in the GO analysis were mainly enriched in gene expression and transcription regulation,and in the KEGG analysis were enriched in cancer pathway,lipid and atherosclerosis pathway and thyroid tumor pathway.Six key genes,HRas proto-oncogene(HRAS),tumor protein p53(TP53),interleukin 6(IL-6),tumor necrosis factor(TNF),prostaglandin-endoperoxide synthase 2(PTGS2)and peroxisome proliferator activated receptor gamma(PPARG),were screened through the PPI network.Conclusion HRAS,TP53,IL6,TNF,PTGS2 and PPARG may be the targets of EDCs,suggesting that gene mutation,immune and inflammatory response,and abnormal lipid metabolism play important roles in the development of TC.
万方数据
维普
