基于人类蛋白质组微阵列数据筛选蟾毒灵抗癌作用靶点的生物信息学分析  

Bioinformatics analysis for selection of anticancer targets of bufalin based on human proteome microarray data

作　　者：陈光 刘畅颖 宋庆航 孙福林 杨丽娜[1] 李冰[1] CHEN Guang;LIU Changying;SONG Qinghang;SUN Fulin;YANG Lina;LI Bing(Department of Genetics and Cell Biology,Basic Medical College,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学基础医学院遗传学与细胞生物学系,山东青岛266071 [2]青岛大学附属妇女儿童医院超声科,山东青岛266071

出　　处：《青岛大学学报（医学版）》2024年第5期639-646,共8页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金资助项目(81803895,818712-31);山东省自然科学基金资助项目(ZR2021YQ57)。

摘　　要：目的通过生物信息学方法分析蟾毒灵人类蛋白质组微阵列数据,探究蟾毒灵互作蛋白之间的潜在联系,预测蟾毒灵在癌症中的作用靶点。方法使用clusterProfiler包进行GO、KEGG和GSEA富集分析,使用STRING数据库及Cytoscape软件进行关键蛋白筛选。下载TCGA数据库数据进行关键基因的泛癌分析;使用survival包绘制关键基因在肺癌、肝癌和胃癌中的K-M曲线,评估其预后效能。结果GO、KEGG和GSEA富集分析结果表明,蟾毒灵潜在互作蛋白显著富集于细胞内的各类囊泡的腔和膜以及核糖体等细胞组分,与鸟苷核苷酸结合、GTP结合、钙黏蛋白结合等分子功能以及氨基酸及衍生物代谢、糖代谢、核糖体、真核细胞翻译起始、细胞周期、细胞凋亡、DNA复制等生物学过程密切相关。筛选出前10位的核心蛋白,分别为RPL6、RPL8、RPL14、RPL24、RPL31、RPL36、RPS4X、RPS16、FAU和GNB2L1,其中除GNB2L1外均为核糖体蛋白。TCGA数据库分析结果表明,核心蛋白中的9种核糖体蛋白在大多数癌症中差异表达且与我国死亡率前3位的癌症肺癌、肝癌和胃癌的预后密切相关。结论蟾毒灵可能通过与核糖体蛋白直接相互作用调控癌细胞中核糖体的组装与发生,阻碍其蛋白合成从而发挥抑癌作用。Objective To analyze the human proteome microarray data of bufalin using the bioinformatics method,to explore the potential interactions between bufalin and proteins,and to predict the targets of bufalin in cancer treatment.Methods ClusterProfiler package was used for GO,KEGG,and GSEA enrichment analyses.STRING database and Cytoscape software were used to screen for key proteins.Data from TCGA were used for pan-cancer analysis of key genes.The K-M curves of key genes in lung cancer,liver cancer,and gastric cancer were plotted using the survival package to evaluate the prognostic efficacy.Results GO,KEGG,and GSEA enrichment analyses showed that the proteins interacting with bufalin were significantly enriched in the cellular components such as lumen and membrane of various vesicles and in ribosome.These proteins were closely related to mole-cular functions such as guanosine nucleotide binding,GTP binding,and cadherin binding as well as biological processes such as amino acid and derivative metabolism,glucose metabolism,ribosome,eukaryotic translation initiation,cell cycle,apoptosis,and DNA replication.The top ten core proteins were RPL6,RPL8,RPL14,RPL24,RPL31,RPL36,RPS4X,RPS16,FAU,and GNB2L1,which were ribosomal proteins except GNB2L1.Analysis using TCGA database showed that the nine ribosomal core proteins were differentially expressed in most cancers and were closely related to the prognosis of the top three cancers for mortality in China(lung cancer,liver cancer,and gastric cancer).Conclusion Bufalin may regulate the assembly and occurrence of ribosomes in cancer cells through direct interaction with ribosomal proteins,which hinders the protein synthesis in cancer cells and thus cancer growth.

关 键 词：肿瘤 蟾毒灵 蛋白质阵列分析 计算生物学 

分 类 号：R394-33[医药卫生—医学遗传学]