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Analysis of gene expression and methylation datasets identified ADAMTS9, FKBP5, and PFKBF3 as biomarkers for osteoarthritis
Author(s) -
Li ZhaoFang,
Zhang RongQiang,
Yang XiaoLi,
Zhang DanDan,
Li BaoRong,
Zhang Di,
Li Qiang,
Xiong YongMin
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27557
Subject(s) - osteoarthritis , fkbp5 , methylation , gene , gene expression , computational biology , biology , bioinformatics , biomarker , dna methylation , genetics , medicine , pathology , alternative medicine , glucocorticoid receptor
Background: Osteoarthritis (OA) is a kind of chronic osteoarthropathy and degenerative joint disease. Epigenetic regulation in the gene expression dynamics has become increasingly important in OA. We performed a combined analysis of two types of microarray datasets (gene expression and DNA methylation) to identify methylation‐based key biomarkers to provide a better understanding of molecular biological mechanisms of OA.Methods: We obtained two expression profiling datasets (GSE55235, GSE55457) and one DNA methylation profiling data set (GSE63695) from the Gene Expression Omnibus. First, differentially expressed genes (DEGs) between patients with OA and controls were identified using the Limma package in R(v3.4.4). Then, function enrichment analysis of DEGs was performed using a DAVID database. For DNA methylation datasets, ChAMP methylation analysis package was used to identify differential methylation genes (DMGs). Finally, a comprehensive analysis of DEGs and DMGs was conducted to identify genes that exhibited differential expression and methylation simultaneously.Results: We identified 112 DEGs and 2,896 DMGs in patients with OA compared with controls. Functional analysis of DEGs obtained that inflammatory responses, immune responses, and positive regulation of apoptosis, tumor necrosis factor (TNF) signaling pathway, and osteoclast differentiation may be involved in the pathogenesis of OA. Cross‐analysis revealed 26 genes that exhibited differential expression and methylation in OA. Among them, ADAMTS9, FKBP5, and PFKBF3 were identified as valuable methylation‐based biomarkers for OA.Conclusion: In summary, our study identified different molecular features between patients with OA and controls. This may provide new clues for clarifying the pathogenetic mechanisms of OA.