先天性纯红细胞再生障碍性贫血氧化应激相关差异表达基因的生物信息学分析  

Identification of Key Genes and Pathways Associated with DBA by Bioinformatics Analysis

作　　者：夏悦昕 刘志远 宋文倩[1] 邵林楠 梁晓华[1] 周世航[1] XIA Yue-xin;LIU Zhiyuan;SONG Wen-qian(Dalian Blood Center,Dalian 116000)

机构地区：[1]大连市血液中心,辽宁大连116000 [2]大连市妇女儿童医疗中心(集团)儿童医院院区

出　　处：《临床输血与检验》2023年第1期82-87,共6页Journal of Clinical Transfusion and Laboratory Medicine

摘　　要：目的筛选先天性纯红细胞再生障碍性贫血(diamond-blackfan anemia,DBA)氧化应激相关差异基因,以及关键信号通路,为深入研究DBA的分子机制提供新的切入点。方法采用GEO数据库的mRNA表达芯片数据GSE14335,利用R语言limma包,筛选DBA患者和健康对照组的差异表达基因(DEGs),从Gene Cards数据库筛选氧化应激相关基因(OSGs),利用R语言VennDiagram包获得氧化应激相关差异表达基因(DE-OSGs)。应用R语言ClusterProfiler包,对DEOSGs进行GO分析和KEGG富集分析。通过Cytoscape构建PPI蛋白质相互作用网络,筛选核心基因。结果筛选出DBA患者和健康对照差异表达基因372个,与氧化应激相关的基因有40个,其中7个基因表达下调,33个基因表达上调。KEGG富集分析发现,氧化应激相关差异表达基因涉及到的信号通路主要有TNF信号通路、AGE-RAGE信号通路、IL-17信号通路、NF-κB信号通路、Toll样受体等。获得10个核心靶标:IL6、PPARG、CCL2、PTGS2、CXCL8、ICAM1、NFKBIA、EDN1、HMOX1和CXCL1。结论本研究通过生物信息学方法,获得DBA氧化应激相关关键基因和相关信号通路,关键基因可能成为DBA研究的新的靶点,为研究DBA的发病机制提供了新的切入点。Objective The current study aimed to identify critical genes and pathways in order to unravel the molecular mechanisms associated with Diamond-Blackfan Anemia(DBA).Method The gene expression profile dataset(GSE14335)was downloaded from Gene Expression Omnibus(GEO)database.The“limma”package in R software was utilized to identify the differentially expressed oxidative stress associated genes(DE-OSGs).“Cluster Profiler”package in R software was used for Gene ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of DE-OSGs.Protein-protein interaction(PPI)network was constructed with STRING and hub genes were screened by Cytoscape.Result Totally 372 DEGs,including 40 DE-OSGs,were screened in this study.DE-OSGs were mainly enriched in TNF signaling pathway,AGE-RAGE signaling pathway in diabetic complications,IL-17 signaling pathway,NF-kappa B signaling pathway,and Toll-like receptor signaling pathway.The top 10 hub genes of PPI network were IL6,PPARG,CCL2,PTGS2,CXCL8,ICAM1,NFKBIA,EDN1,HMOX1 and CXCL1.Conclusion The present study identified the DE-OSGs and pathways in DBA by bioinformatics analysis,which may provide novel insights for unraveling pathogenesis of DBA.The hub genes might serve as biomarkers for diagnosis and treatment.

关 键 词：先天性纯红细胞再生障碍性贫血 生物信息学分析 差异表达基因 氧化应激 

分 类 号：R556[医药卫生—血液循环系统疾病]