摘要
目的 综合生物信息学方法分析绝经后骨质疏松(Postmenopausal osteoporosis, PMOP)的差异表达基因及免疫浸润机制,并预测治疗PMOP的潜在中药。方法 通过检索GEO数据库获取GSE56116数据集,利用R语言鉴别差异表达基因(DEG)。利用STRING在线平台构建蛋白互作网络图(PPI),并通过Cytoscape 3.7.2软件进一步构建核心靶点网络图。应用DAVID数据库对差异基因进行GO功能和KEGG富集分析。CIBERSORT用于评估PMOP中免疫细胞的浸润。利用医学本体信息检索平台与差异基因相互映射,预测治疗PMOP的潜在中药。结果 共鉴定出971个DEG,其中包括541个上调基因,430个下调基因,并通过Cytoscape 3.7.2软件筛选得到SYK、FOS、LYN、IL4、HSPG2、ITGB1、RXRA、HCK等可能是与PMOP相关系的核心靶点。GO功能富集主要与甾醇代谢过程(Sterol metabolic process)、胆固醇代谢过程(Cholesterol metabolic process)、肽结合(Peptide binding)、产生超氧化物的NADPH氧化酶激活剂活性(Superoxide-generating NADPH oxidase activator activity)等生物功能相关。KEGG富集分析靶点主要富集在NF-kB信号通路(NF-kappa B signaling pathway)、fcεRI信号通路(Fc epsilon RI signaling pathway)、刺猬信号通路(Hedgehog signaling pathway)、MAPK信号通路(MAPK signaling pathway)、戊糖磷酸途径(Pentose phosphate pathway)等信号通路中。人参、三七、石斛、姜黄可能成为治疗PMOP的潜在候选中药。结论 利用综合生物信息学鉴别DEG、信号通路和免疫浸润有助于理解PMOP的发病机制,为理解与PMOP发生和发病相关的分子机制提供了理论依据,并为进一步探索中药治疗PMOP的作用机制提供了研究方法与策略。
Objective To analyze differentially expressed genes(DEGs)and the immune infiltration mechanism of postmenopausal osteoporosis(PMOP)by comprehensive bioinformatics methods, and to predict potential Chinese medicines for treating PMOP.Methods GSE56116 data set was obtained by searching gene expression omnibus(GEO)database, and DEGs were identified by R language.The network diagrams of protein-protein interaction(PPI)and core targets were constructed by STRING and Cytoscape3.7.2,respectively.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of DEGs were performed in the database for annotation, visualization and integrated discovery(DAVID).CIBERSORT was employed to evaluate the infiltration of immune cells in PMOP.Based on the mutual mapping between Coremine Medical and DEGs, potential Chinese medicines for treating PMOP were predicted.Results A total of 971 DEGs were identified, including 541 up-regulated genes and 430 down-regulated genes.SYK,FOS,LYN,IL4,HSPG2,ITGB1,RXRA,and HCK screened by Cytoscape3.7.2 might be the core targets related to PMOP.The functional enrichment of GO was mainly correlated with the biological functions such assterol metabolic process, cholesterol metabolic process, peptide binding and superoxide-generating NADPH oxidase activator activity.KEGG enrichment analysis showed that targets are mainly enriched in nuclear factor kappa B(NF-kB),Fc epsilon RI(fcεRI),hedgehog, mitogen-activated protein kinase(MAPK),and pentose phosphate signalling pathways.Radix Ginseng, Radix et Rhizoma Notoginseng, Herba Dendrobii andRhizoma Curcumae Longaewere potential candidates for treating PMOP.Conclusion Identificationof DEGs, signalling pathway and immune infiltration by comprehensive bioinformatics is helpful to understand the pathogenesis of PMOP,which provides theoretical basis for understanding the molecular mechanisms responsible for the occurrence and pathogenesis of PMOP,and suggests research methods and strategies for further exploring the mechanisms of C
作者
方梦泽
李志超
薛海鹏
徐展望
FANG Meng-ze;LI Zhi-chao;XUE Hai-peng;XU Zhan-wang(Shandong University of Traditional Chinese Medicine,Jinan Shandong250014;The Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan Shandong250014)
出处
《世界中西医结合杂志》
2022年第3期447-453,460,共8页
World Journal of Integrated Traditional and Western Medicine
基金
国家自然科学基金资助项目(8217151988)
山东省自然科学基金重点项目(ZR202011050051)。
关键词
绝经后骨质疏松
生物信息学
差异基因
免疫浸润
中药预测
Postmenopausal osteoporosis
Bioinformatics
Differentially expressed gene
Immune infiltration
Chinese medicine forecast
