Identification of abnormally methylated–differentially expressed genes and pathways in osteoarthritis: a comprehensive bioinformatic study
Identification of abnormally methylated–differentially expressed genes and pathways in osteoarthritis: a comprehensive bioinformatic study
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DOI：
10.1007/s10067-020-05539-w
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Puyi Sheng
中科院分区：
文献类型：
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作者：
Linli Zheng;Weishen Chen;Guoyan Xian;Baiqi Pan;Yongyu Ye;Minghui Gu;Yinyue Ma;Ziji Zhang;Puyi Sheng
Objectives To investigate abnormally methylated–differentially expressed genes (DEGs) and their related pathways in osteoarthritis.(OA) by comprehensive bioinformatic analysis..Methods Gene expression profiles of GSE51588 and GSE114007, and a gene methylation microarray data GSE63695 were.downloaded from the Gene Expression Omnibus (GEO) repository. Abnormally methylated DEGs were identified. Gene.Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of these genes were.subsequently performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The proteinprotein.interaction (PPI) network was built from STRING.Module analysis and hub gene identification were performed by using.Cytoscape. Co-expression analysis was also constructed using the CEMiTool package..Results In total, 133 abnormally methylated DEGs were identified, including 85 hypomethylation high-expression genes and 48.hypermethylation low-expression genes. Among biological processes and KEGG pathways of abnormally methylated DEGs,.collagen fibril organization was enriched most frequently, and pathways of oxidative stress and aging were enriched, including.HIF-1 signaling pathway, AMPK signaling pathway, and FoxO signaling pathway. In PPI networks, the hub genes of hypomethylation.high-expression genes were COL1A1, COL3A1, COL1A2, COL5A2, LUM, MMP2, SPARC, COL2A1, COL6A2,.and COL7A1, and the hub genes of hypermethylation low-expression genes were VEGFA, SLC2A1, LDHA, PDK1, and.BNIP3. Combined with co-expression analysis, COL3A1, LUM, and MMP2 were the critical hypomethylation highexpression.hub genes in medial tibia subchondral bone..Conclusions Our study implied abnormally methylated DEGs and dysregulated pathways in OA. Common methylation biomarkers.included COL3A1, LUM, andMMP2, and we also found that THBS2 may serve as a novel biomarker in end-stage OA.
