Screening of gene signatures for rheumatoid arthritis and osteoarthritis based on bioinformatics analysis.
Screening of gene signatures for rheumatoid arthritis and osteoarthritis based on bioinformatics analysis.
复制标题
基于生物信息学分析的类风湿关节炎和骨关节炎基因特征筛选
DOI：
10.3892/mmr.2016.5423
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发表时间：
2016-08
影响因子：
3.4
通讯作者：
Kang Y
中科院分区：
文献类型：
--
作者：
He P;Zhang Z;Liao W;Xu D;Fu M;Kang Y
目前的研究旨在确定类风湿性关节炎（RA）和骨关节炎（OA）的基因签名，并使用这些来阐明潜在的模块化机制。使用基因表达Omnibus数据库，本研究获得了来自RA和OA滑膜成纤维细胞的GSE 7669 mRNA表达微阵列数据（各n=6）。使用微阵列分析软件包的线性模型，在RA滑膜样本与OA样本相比，差异表达的基因（DEG）进行了鉴定。使用用于注释可视化和集成发现的数据库进行基因本体和京都基因百科全书和基因组途径富集分析。构建了蛋白质-蛋白质相互作用网络，并使用Cytoscape的分子复合物检测插件对模块进行了进一步分析。通过比较RA和OA滑膜样本，共鉴定出181个DEG（96个上调基因和85个下调基因）。模块1中的显著DEG，包括胶原蛋白，I型，α 1（COL 1A 1），COL 3A 1，COL 4A 1和COL 11 A1，主要富集在细胞外基质（ECM）-受体相互作用和粘着斑途径中。此外，模块2中的重要DEG，包括含自由基S-腺苷甲硫氨酸结构域2（RSAD 2）、2′-5′-寡腺苷酸合成酶2（OAS 2）、粘病毒（流感病毒）抗性1（MX 1）和ISG 15泛素样修饰物（ISG 15），主要与免疫功能途径相关。总之，本研究表明RSAD 2，OAS 2，MX 1和ISG 15可能是通过调节免疫应答而在RA发展中的显著基因特征。COL 3A 1、COL 4A 1、COL 1A 1和COL 11 A1可能通过参与ECM-受体相互作用和局灶性粘连的途径而在OA的发展中起重要作用。
The current study aimed to identify gene signatures during rheumatoid arthritis (RA) and osteoarthritis (OA), and used these to elucidate the underlying modular mechanisms. Using the Gene Expression Omnibus database, the present study obtained the GSE7669 mRNA expression microarray data from RA and OA synovial fibroblasts (n=6 each). The differentially expressed genes (DEGs) in RA synovial samples compared with OA samples were identified using the Linear Models for Microarray Analysis package. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation Visualization and Integrated Discovery. A protein-protein interaction network was constructed and the modules were further analyzed using the Molecular Complex Detection plugin of Cytoscape. A total of 181 DEGs were identified by comparing RA and OA synovial samples (96 up- and 85 downregulated genes). The significant DEGs in module 1, including collagen, type I, α 1 (COL1A1), COL3A1, COL4A1 and COL11A1, were predominantly enriched in the extracellular matrix (ECM)-receptor interaction and focal adhesion pathways. Additionally, significant DEGs in module 2, including radical S-adenosyl methionine domain containing 2 (RSAD2), 2′-5′-oligoadenylate synthetase 2 (OAS2), myxovirus (influenza virus) resistance 1 (MX1) and ISG15 ubiquitin-like modifier (ISG15), were predominantly associated with immune function pathways. In conclusion, the present study indicated that RSAD2, OAS2, MX1 and ISG15 may be notable gene signatures in RA development via regulation of the immune response. COL3A1, COL4A1, COL1A1 and COL11A1 may be important gene signatures in OA development via involvement in the pathways of ECM-receptor interactions and focal adhesions.