人类风湿关节炎滑膜中ABC转运蛋白基因差异表达的生物信息学分析  

Bioinformatics analysis of the expression of ATP binding cassette transporters in human rheumatoid synovium

作　　者：郑婷丹 刘倩楠 张涵旭 潘越 吴昊[1,2] 付英梅 宋武琦[1,2] Zheng Tingdan;Liu Qiannan;Zhang Hanxu;Pan Yue;Wu Hao;Fu Yingmei;Song Wuqi(Department of Microbiology,Wu Lien-Teh Institute,Harbin Medical University,Harbin 150081,China)

机构地区：[1]哈尔滨医科大学微生物学教研室,哈尔滨150081 [2]伍连德研究所,哈尔滨150081

出　　处：《国际遗传学杂志》2022年第4期265-274,共10页International Journal of Genetics

基　　金：国家重大科技产业工程计划(2017YFB0403805)。

摘　　要：目的本研究通过对来自GEO数据库的数据和实验室测序数据进行生物信息学分析,分析ATP结合盒(ATP-binding cassette,ABC)转运蛋白基因在类风湿关节炎中的表达情况,分析ABC转运蛋白在类风湿关节炎中的作用机制。方法采用R语言软件对人类风湿关节炎(rheumatoid arthritis,RA)、骨关节炎(osteoarthritis,OA)滑膜组织以及正常(normal,N)滑膜组织,体外实验中的人类滑膜成纤维细胞中肿瘤坏死因子(tumor necrosis factor-α,TNF-α)实验组和对照组的多基因差异表达谱数据集进行综合分析。将ABC转运蛋白的差异基因与其他差异基因相关联,以获得相关性更大的差异基因。使用KEGG对具有更高相关性的差异表达基因(differentially expressed genes,DEGs)进行通路富集。利用Cytospace软件的STRING在线数据库,通过蛋白质相互作用(PPI)网络分析鉴定枢纽(Hub)基因。结果ABC转运蛋白基因差异表达:RA组与N组相比,ABCC4和ABCG1的表达显著增加,而ABCA8的表达显著降低(P<0.001);RA组与OA组相比,ABCC4的表达显著增加,ABCA8的表达显著降低(P<0.001);与对照组相比,TNF-α组ABCA5的表达显著增加。与上述ABC家族具有高度相关性的差异表达基因的KEGG通路和蛋白质相互作用(PPI)网络分析进一步发现,大多数已确定的通路参与炎症、增殖、细胞存活和血管生成的调节。结论本研究发现了在类风湿关节炎中潜在的一组ABC家族差异基因,这将为RA的早期诊断提供潜在的生物标志物,并将有助于研究ABC转运蛋白在RA中的作用机制以及分子靶向治疗。Objective Here we performed bioinformatics analysis of data from GEO to investigate the expression of ATP-binding cassette(ABC)transporter genes and its role in the pathogenesis of rheumatoid arthritis(RA).Methods R software was used to perform integral analysis of the data sets of multiple gene dfferential expression profiles in RA tissues,osteoarthritis(OA)tissues and normal synovial tissues(N)in vivo as well as TNF experimental group and control group in vitro in human synovial fibroblasts.The differential genes of ABC transporters were correlated with other differential genes to obtain differential genes with greater correlation.Kyoto Encyclopedia of Genes and Genomes(KEGG)path analysis was done for differentially expressed genes(DEGs)with greater correlation.Hub genes were identified by protein interaction(PPI)network analysis using the STRING online database with Cytospace software.Results For the differential genes of ABC transporters:the expression of ABCC4 and ABCG1 were significantly increased in RA vs.N group,while the expression of ABCA8 was significantly decreased(P<0.001);the expression of ABCC4 was significantly increased in RA vs.OA group,and the expression of ABCA8 was significantly decreased(P<0.001);the expression of ABCA5 was significantly increased in TNF vs.control group(P<0.001).The Kyoto Encyclopedia of Genes and Genomes(KECG)pathway and protein interaction(PPI)network involved in the differentially expressed genes(DEGs)of the aforementioned ABC family with large correlation were further detected to be associated with RA pathogenesis.Conclusion This study identified a novel set of potentially critical ABC family differential genes in RA,which provide potential biomarkers for early diagnosis and will facilitate the study on the mechanism underlying actions of ABC transporters in RA and molecular targeted therapy for RA.

关 键 词：类风湿关节炎 ABC转运蛋白 GEO数据库 生物标志物 生物信息学 

分 类 号：R593.22[医药卫生—内科学]