肝细胞癌外周血单个核细胞关键基因与治疗中药的生信分析及系统评价  

Key Genes of Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma and Effective Chinese Herbs:A Bioinformatics Analysis and Systematic Review

作　　者：高云霄 杨柳[1] 李泽 王杰[1] 贾雪梅 郭榆西 李博林 王小天[2] GAO Yun-xiao;YANG Liu;LI Ze;WANG Jie;JIA Xue-mei;GUO Yu-xi;LI Bo-lin;WANG Xiao-tian(Graduate School,Hebei University of Chinese Medicine,Shijiazhuang 050090,China;The First Affiliated Hospital of Hebei University of Chinese Medicine,Shijiazhuang 050011,China)

机构地区：[1]河北中医学院研究生院,石家庄050090 [2]河北中医学院第一附属医院,石家庄050011

出　　处：《中国实验方剂学杂志》2021年第20期162-171,共10页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家科技部重点研发计划项目(2018YFC1704102);河北省科技计划项目(21377724D,21377740D)。

摘　　要：目的:基于生物信息学的方法探索肝细胞癌外周血单个核细胞(HCC-PBMC)的关键基因和潜在的治疗中药,并通过系统评价进一步确认该药的临床疗效。方法:利用基因表达数据库(GEO)下载关于HCC-PBMC的芯片GSE58208和GSE36076。通过RStudio软件分析获得差异表达基因(DEGs)。利用STRING在线数据库进行蛋白-蛋白相互作用(PPI)分析,DAVID在线功能注释工具进行基因本体(GO)和京都基因和基因组百科全书(KEGG)富集分析。通过Cytoscape软件对HCCPBMC差异基因进行可视化,同时,利用CytoHubba插件计算出HCC-PBMC的关键基因。通过将关键基因与医学信息检索平台相互映射,筛选出治疗肝细胞癌(HCC)的潜在中药并纳入下一步的系统评价。结果:共得出203个DEGs(上调基因194个,下调基因9个)。经DAVID分析,可知这些DEGs主要富集的生物学过程和信号通路包括DNA模板转录调控、核糖核酸磷酸二酯键水解,核内裂解、核分裂的正调控、骨骼肌纤维发育、丝裂原活化蛋白激酶(MAPK)活性的激活、范可尼贫血途径、代谢途径。通过Cytoscape软件计算出HCC-PBMC的关键基因,分别是GTP酶IMAP家族成员1(GIMAP1),GTP酶IMAP家族成员4(GIMAP4),GTP酶IMAP家族成员6(GIMAP6),GTP酶IMAP家族成员7(GIMAP7),GTP酶IMAP家族成员8(GIMAP8),白细胞介素-1β(IL-1β),趋化因子(CX3C基元)受体1(CX3CR1),趋化因子(C-C基元)受体2(CCR2),Toll样受体7(TLR7),表皮生长因子(EGF)。经Coremine Medical分析得出人参、姜黄、积雪草、白花蛇舌草与关键基因关系较为密切,其中人参具有补益肺脾、增强气力功效,与HCC肝郁脾虚、气阴两虚证相符合,故将以人参为君药的四君子汤纳入系统评价。经过评价得出人参在提高临床总体疗效,改善患者中医证候及血清CD4+,CD4+/CD8+水平,降低患者血清CD8+,总胆红素(TBIL)水平方面均优于单纯西医治疗(P<0.01),且安全性高。结论:本研究基于基因层面展开分析,�Objective:To explore the key gens of peripheral blood mononuclear cells in hepatocellular carcinoma(HCC-PBMC)and potentially effective Chinese herbs based on bioinformatics,and to verify the clinical efficacy of these Chinese herbs via a systematic review. Method: The chips GSE58208 and GSE36076 of HCC-PBMC were downloaded from the Gene Expression Omnibus(GEO),followed by the identification of differentially expressed genes(DEGs) using RStudio. After protein-protein interaction(PPI) analysis by STRING,the DAVID was employed for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis. The DEGs of HCC-PBMC were visualized by Cytoscape. The key genes of HCCPBMC were calculated by CytoHubba plug-in and mapped with those in Coremine Medical for screening out the potential Chinese herbs for the treatment of HCC,which were then included for subsequent systematic review.Result: A total of 203 DEGs were obtained(194 up-regulated and nine down-regulated). As revealed by DAVID analysis,the DEGs were mainly enriched in such biological processes and signaling pathways as transcriptional regulation of DNA template, hydrolysis of ribonucleic acid phosphodiester bond, positive regulation of intranuclear mitosis and division, skeletal muscle fiber development, activation of mitogenactivated protein kinase(MAPK)activity,Fanconi anemia pathway,and metabolic pathway. The key genes of HCC-PBMC were calculated by Cytoscape to be GTPase IMAP family member 1(GIMAP1),GTPase IMAP family member 4(GIMAP4),GTPase IMAP family member 6(GIMAP6),GTPase IMAP family member 7(GIMAP7),GTPase IMAP family member 8(GIMAP8),interleukin-1β(IL-1β),CX3 C chemokine receptor 1(CX3 CR1),C-C chemokine receptor type 2(CCR2),Toll-like receptor 7(TLR7),and epidermal growth factor(EGF). Through Coremine Medical analysis,it was concluded that Ginseng Radix et Rhizoma,Curcumae Longae Rhizoma,Centellae Herba,and Hedyotidis Herba were closely related to the key genes. Ginseng Radix et Rhizoma has the effects of tonifying and benefiting

关 键 词：肝细胞癌外周血单个核细胞 关键基因 中药 生信分析 系统评价 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学]