通过全转录组分析鉴定骨关节炎病理过程中的关键基因。
Global transcriptome analysis to identify critical genes involved in the pathology of osteoarthritis.
作者信息
Zhang X, Bu Y, Zhu B, Zhao Q, Lv Z, Li B, Liu J
机构信息
Department of Joint Surgery, Tianjin Hospital, Tianjin, China.
Department of Sports Medicine and Arthroscopic Surgery, Tianjin Hospital, Tianjin, China.
出版信息
Bone Joint Res. 2018 May 5;7(4):298-307. doi: 10.1302/2046-3758.74.BJR-2017-0245.R1. eCollection 2018 Apr.
OBJECTIVES
The aim of this study was to identify key pathological genes in osteoarthritis (OA).
METHODS
We searched and downloaded mRNA expression data from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) of joint synovial tissues from OA and normal individuals. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were used to assess the function of identified DEGs. The protein-protein interaction (PPI) network and transcriptional factors (TFs) regulatory network were used to further explore the function of identified DEGs. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the result of bioinformatics analysis. Electronic validation was performed to verify the expression of selected DEGs. The diagnosis value of identified DEGs was accessed by receiver operating characteristic (ROC) analysis.
RESULTS
A total of 1085 DEGs were identified. KEGG pathway analysis displayed that Wnt was a significantly enriched signalling pathway. Some hub genes with high interactions such as USP46, CPVL, FKBP5, FOSL2, GADD45B, PTGS1, and ZNF423 were identified in the PPI and TFs network. The results of qRT-PCR showed that GADD45B, ADAMTS1, and TFAM were down-regulated in joint synovial tissues of OA, which was consistent with the bioinformatics analysis. The expression levels of USP46, CPVL, FOSL2, and PTGS1 in electronic validation were compatible with the bio-informatics result. CPVL and TFAM had a potential diagnostic value for OA based on the ROC analysis.
CONCLUSION
The deregulated genes including USP46, CPVL, FKBP5, FOSL2, GADD45B, PTGS1, ZNF423, ADAMTS1, and TFAM might be involved in the pathology of OA.: X. Zhang, Y. Bu, B. Zhu, Q. Zhao, Z. Lv, B. Li, J. Liu. Global transcriptome analysis to identify critical genes involved in the pathology of osteoarthritis. 2018;7:298-307. DOI: 10.1302/2046-3758.74.BJR-2017-0245.R1.
目的
本研究旨在鉴定骨关节炎（OA）中的关键病理基因。
方法
我们从基因表达综合数据库搜索并下载mRNA表达数据，以鉴定OA患者和正常个体关节滑膜组织中的差异表达基因（DEG）。利用基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析来评估鉴定出的DEG的功能。蛋白质-蛋白质相互作用（PPI）网络和转录因子（TF）调控网络用于进一步探索鉴定出的DEG的功能。应用定量实时聚合酶链反应（qRT-PCR）验证生物信息学分析结果。进行电子验证以核实所选DEG的表达。通过受试者工作特征（ROC）分析评估鉴定出的DEG的诊断价值。
结果
共鉴定出1085个DEG。KEGG通路分析显示Wnt是一条显著富集的信号通路。在PPI和TF网络中鉴定出一些具有高相互作用的枢纽基因，如USP46、CPVL、FKBP5、FOSL2、GADD45B、PTGS1和ZNF423。qRT-PCR结果显示，OA患者关节滑膜组织中GADD45B、ADAMTS1和TFAM表达下调，这与生物信息学分析结果一致。电子验证中USP46、CPVL、FOSL2和PTGS1的表达水平与生物信息学结果相符。基于ROC分析，CPVL和TFAM对OA具有潜在诊断价值。
结论
包括USP46、CPVL、FKBP5、FOSL2、GADD45B、PTGS1、ZNF423、ADAMTS1和TFAM在内的失调基因可能参与OA的病理过程。：张X、卜Y、朱B、赵Q、吕Z、李B、刘J。全转录组分析以鉴定参与骨关节炎病理过程的关键基因。2018；7：298 - 307。DOI：10.1302/2046 - 3758.74.BJR - 2017 - 0245.R1。
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