Identification of dysregulated genes in rheumatoid arthritis based on bioinformatics analysis.
BACKGROUND
Rheumatoid arthritis (RA) is a chronic auto-inflammatory disorder of joints. The present study aimed to identify the key genes in RA for better understanding the underlying mechanisms of RA.


METHODS
The integrated analysis of expression profiling was conducted to identify differentially expressed genes (DEGs) in RA. Moreover, functional annotation, protein-protein interaction (PPI) network and transcription factor (TF) regulatory network construction were applied for exploring the potential biological roles of DEGs in RA. In addition, the expression level of identified candidate DEGs was preliminarily detected in peripheral blood cells of RA patients in the GSE17755 dataset. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to validate the expression levels of identified DEGs in RA.


RESULTS
A total of 378 DEGs, including 202 up- and 176 down-regulated genes, were identified in synovial tissues of RA patients compared with healthy controls. DEGs were significantly enriched in axon guidance, RNA transport and MAPK signaling pathway. RBFOX2, LCK and SERBP1 were the hub proteins in the PPI network. In the TF-target gene network, RBFOX2, POU6F1, WIPF1 and PFKFB3 had the high connectivity with TFs. The expression status of 11 candidate DEGs was detected in GSE17755, the expression levels of MAT2A and NSA2 were significantly down-regulated and CD47 had the up-regulated tendency in peripheral blood cells of patients with RA compared with healthy individuals. qRT-PCR results of MAT2A, NSA2, CD47 were compatible with our bioinformatics analyses.


CONCLUSIONS
Our study might provide valuable information for exploring the pathogenesis mechanism of RA and identifying the potential biomarkers for RA diagnosis.
Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Ruihu
R
Hao
Department of Bioinformatics, Beijing Medintell Biomed Co., Ltd, Beijing, China.
Haiwei
H
Du
Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Lin
L
Guo
Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Fengde
F
Tian
Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Ning
N
An
Department of Orthopedics, Affiliated Hospital of BeiHua University, Jilin, China.
Tiejun
T
Yang
Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Changcheng
C
Wang
Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Bo
B
Wang
Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Zihao
Z
Zhou
Differentially expressed genes; Integrated analysis; Pathogenesis; Regulatory network; Rheumatoid arthritis