基于CTD数据库的双酚A及其衍生物双酚F和双酚S的生物信息学分析  

Based on the comparative toxicogenomics database bioinformatic analysis of bisphenol A and its analogues bisphenol F and bisphenol S

作　　者：刘福志 朱丹丹 陈扬佳 邓锂峰 肖默 涂卓特 LIU Fu-zhi;ZHU Dan-dan;CHEN Yang-jia;DENG Li-feng;XIAO Mo;TU Zhuo-te(Quanzhou Medical College,Quanzhou Fujian 36201l,China)

机构地区：[1]泉州医学高等专科学校,福建泉州362011

出　　处：《毒理学杂志》2022年第5期442-447,455,共7页Journal of Toxicology

基　　金：泉州市指导性科技计划项目(2021N124S);泉州医学高等专科学校校级科研项目(XJK2009B)。

摘　　要：目的 利用生物信息学技术分析双酚A(bisphenol A, BPA)及其衍生物双酚F(bisphenol F, BPF)、双酚S(bisphenol S, BPS)共同影响的关键信号通路及可能的机制,为BPA及其衍生物BPF、BPS相关研究提供一定的线索和思路。方法 利用比较毒理基因组学数据库(CTD),筛选BPA及其衍生物BPF、BPS共同影响的hub基因,使用可视化和Hipolt在线工具对hub基因进行通路分析,筛选关键基因。结果 获得BPA及其衍生物BPF、BPS共同影响的50个hub基因,其中EGFR基因Degree最高为22。GO和KEGG富集分析,得到具有统计学意义的差异GO条目140个(P<0.05),分别为生物学途径(biological processes, BP)有119个,细胞组分(cellular components, CC)有5个,分子功能(molecular function, MF)有16个,其中BP间有较多交互基因,如EGFR、ESR1和CAV1等。KEGG分析中具有统计学意义差异最高的2条通路,包括膀胱癌(P=3.40×10^(-6))和甲状腺癌(P=5.21×10^(-5)),并且膀胱癌信号通路主要受到EGFR和CDK4等基因的调控。结论 本次基于2021年4月更新的CTD数据库所开展的生物信息学分析提示,BPA及其衍生物BPF、BPS共同暴露可能引起关键基因EGFR改变,EGFR可能通过成纤维细胞增殖影响膀胱癌的发生发展。Objective To analyse the key signaling pathways and potential mechanisms of bisphenol A(BPA) and its analogues bisphenol F(BPF), bisphenol S(BPS) by using bioinformatics technology, and to provide a clue to the related study of BPA and its analogues BPF, BPS. Methods Hub genes jointly affected by BPA and its analogues BPF, BPS were screened based on Comparative Toxicogenomics Database(CTD).Visualization and Hipolt online tool were used for hub genes to carry pathways analysis and choose key genes. Results A total of 50 hub genes jointly affected by BPA and its analogues BPF, BPS were obtained from the database, including the highest Degree of EGFR is 22. Through Gene Ontology(GO) and kyoto Encyclopedia of Genes and Genomes(KEGG) analysis, 140 in GO item were found significantly enriched(P<0.05).There are 119, 5, 16 items in biological processes(BP), cellular components(CC)and molecular function(MF),respectively. Among them, there are a lot of interaction genes in BP item, such as EGFR, ESR1 and CAV1.There are the highest significance of two pathways in the KEGG analysis, including bladder cancer(P=3.40×10^(-6))and Thyroid cancer(P=5.21×10^(-5)), and bladder cancer signaling pathway is mainly influenced by EGFR and CDK4. Conclusion The bioinformatics analysis based on updated in April 2021 of CTD database suggest that the exposure between BPA and its derivatives BPF, BPS may change the key genes of EGFR,and EGFR may affect the incidence of bladder cancer by fibroblast proliferation.

关 键 词：双酚A 双酚F 双酚S 比较毒理基因组学数据库 生物信息学分析 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]