| 摘要: |
| 目的 通过生物信息学策略探索强直性脊柱炎（AS）相关的差异基因，寻找疾病的新型诊断标志物。方法 通过美国国立生物技术信息中心的基因表达汇编（GEO）数据库下载AS相关的芯片数据，分析筛选出AS患者和健康人外周血之间的差异表达基因，利用注视、可视化和集成发现数据库（DAVID）对差异表达基因进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）信号通路分析，然后利用在线数据库String构建蛋白质-蛋白质相互作用（PPI）网络，利用Cytoscape 3.7.1软件筛选PPI网络中显著的蛋白质模块获取关键基因。计算ROC曲线的AUC值，评估关键基因对AS的诊断效能。结果 共筛选出187个差异表达基因，其中包含96个上调基因和91个下调基因。GO功能分析结果显示差异表达基因参与的生物学过程主要为核糖核苷一磷酸代谢过程、核苷一磷酸代谢过程和嘌呤核糖核苷一磷酸代谢过程等，KEGG信号通路分析结果显示差异表达基因参与的主要信号通路富集于非酒精性脂肪肝、亨廷顿病和氧化磷酸化等。基于PPI网络分析结果筛选出5个关键基因：ATP合成酶H＋转运线粒体F0复合体亚基F6（ATP5J）、NADH：泛醌氧化还原酶亚基B3（NDUFB3）、泛醇-细胞色素c还原酶结合蛋白（UQCRB）、细胞色素c氧化酶亚基7A2（COX7A2）、泛醇-细胞色素c还原酶铰链蛋白（UQCRH）。它们对AS的诊断效能显著，AUC值分别为0.859、0.852、0.840、0.820、0.805。结论 ATP5J、NDUFB3、UQCRB、COX7A2和UQCRH也许可作为外周血AS疾病相关的新型诊断标志物。 |
| 关键词: 强直性脊柱炎 基因表达汇编 生物信息学 差异表达基因 生物学标志物 |
| DOI：10.16781/j.CN31-2187/R.20211281 |
| 投稿时间：2021-12-20修订日期：2022-05-16 |
| 基金项目:国家自然科学基金(81572201). |
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| Screening hub genes as diagnostic biomarkers for ankylosing spondylitis: a bioinformatics analysis |
| WANG Chen-feng,LU Xu-hua* |
(Department of Orthopaedics, The Second Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200003, China
*Corresponding author) |
| Abstract: |
| Objective To explore the differentially expressed genes (DEGs) related to ankylosing spondylitis (AS) through bioinformatics strategies,and to find new diagnostic markers for the disease.Methods The microarray data related to AS were downloaded from the Gene Expression Omnibus (GEO) database of the National Center of Biotechnology Information,and the DEGs between the AS patients and healthy population in the peripheral blood were analyzed and screened.The Database for Annovation,Visualization,and Integrated Discovery (DAVID) was used to complete the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses of the DEGs,and then the online database String was used to construct a protein-protein interaction (PPI) network,and the Cytoscape 3.7.1 software was used to screen the significant protein modules in the PPI network to obtain hub genes.The area under curve (AUC) values of the receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic efficacy of hub genes for AS.Results A total of 187 DEGs were screened out,including 96 up-regulated genes and 91 down-regulated genes.The results of GO function analysis showed that the DEGs were mainly involved in ribonucleoside monophosphate metabolism process,nucleoside monophosphate metabolism process and purine ribonucleoside monophosphate metabolism process.And the results of KEGG signaling pathway analysis showed that DEGs mainly participated in non-alcoholic fatty liver disease,Huntington's disease and oxidative phosphorylation.Five hub genes (adenosine triphosphate synthase,H+ transporting,mitochondrial F0 complex,subunit F6[ATP5J],NADH:ubiquinone oxidoreductase subunit B3[NDUFB3],ubiquinol-cytochrome c reductase binding protein[UQCRB],cytochrome c oxidase subunit 7A2[COX7A2],and ubiquinol-cytochrome c reductase hinge protein[UQCRH]) were screened out based on the results of PPI network analysis,showing significant diagnostic efficacy for AS (AUC values were 0.859,0.852,0.840,0.820,and 0.805,respectively).Conclusion ATP5J,NDUFB3,UQCRB,COX7A2 and UQCRH may be used as new diagnostic markers related to AS in peripheral blood. |
| Key words: ankylosing spondylitis Gene Expression Omnibus bioinformatics differentially expressed genes biomarkers |
