Identification of key genes and expression profiles in osteoarthritis by co-expressed network analysis. (April 2020)

• Record Type: Journal Article
• Authors: Zhu, Naiqiang; Zhang, Peng; Du, Lilong; Hou, Jingyi; Xu, Baoshan
• Is Part Of: Computational biology and chemistry. Volume 85(2020)
• Publication Date: 2020-04
• Subjects: ATG13 autophagy-related protein 13 -- BAK1 bcl-2 homologous antagonist/killer -- BCS1L mitochondrial chaperone BCS1 -- BP biological process -- CC cellular component -- CLDN5 claudin-5 -- CNOT6 CCR4-NOT transcription complex subunit 6 -- COPZ1 coatomer subunit zeta-1 -- DEGs differentially expressed genes -- ELSPBP1 epididymal sperm-binding protein 1 -- EXD3 exonuclease mut-7 homolog -- FC fold change -- GEO Gene Expression Omnibus -- GO gene ontology -- GOT2 aspartate aminotransferase -- GS gene significance -- GSEA gene set enrichment analysis -- KEGG Kyoto Encyclopedia of Genes and Genomes -- ME module eigengene -- MF molecular function -- MISP mitotic interactor and substrate of PLK1 -- MS module significant -- MSR1 macrophage scavenger receptor types I and II -- OA osteoarthritis -- OCRL inositol polyphosphate 5-phosphatase OCRL-1 -- TAF11 transcription initiation factor TFIID subunit 11 -- TOM topological overlap matrix -- WGCNA weighted gene co-expression network analysis; Osteoarthritis -- Co-expression -- WGCNA -- Differentially expressed genes -- Hub gene -- Bioinformatics analysis -- Biological makers; Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2020.107225
• Languages: English
• ISSNs: 1476-9271

Abstract

Graphical abstract: Highlights: WGCNA was employed to identify highly correlated gene modules associated with OA synovial membrane. The genes in significant module were enriched in the FoxO signaling pathway, and the metabolism of fatty acids and 2-oxocarboxylic acid. 13 hub genes correlated to the development and progression of OA were identified. Abstract: Background: The underlying molecular characteristics of osteoarthritis (OA), a common age-related joint disease, remains elusive. Here, we aimed to identify potential early diagnostic biomarkers and elucidate underlying mechanisms of OA using weighted gene co-expression network analysis (WGCNA). Material and methods: We obtained the gene expression profile dataset GSE55235, GSE55457, and GSE55584, from the Gene Expression Omnibus. WGCNA was used to investigate the changes in co-expressed genes between normal and OA synovial membrane samples. Modules that were highly correlated to OA were subjected to functional enrichment analysis using the R clusterProfiler package. Differentially expressed genes (DEGs) between the two samples were screened using the "limma" package in R. A Venn diagram was constructed to intersect the genes in significant modules and DEGs. RT -PCR was used to further verify the hub gene expression levels between normal and OA samples. Results: The preserved significant module was found to be highly associated with OA development and progression ( P < 1e-200, correlation = 0.92). Functional enrichment analysis suggested that the antiquewhite4 module was highly correlated to FoxO signaling pathway, and the metabolism of fatty acids and 2-oxocarboxylic acid. A total of 13 hub genes were identified based on significant module network topology and DEG analysis, and RT-PCR confirmed that these genes were significantly increased in OA samples compared with that in normal samples. Conclusions: We identified 13 hub genes correlated to the development and progression of OA, which may provide new biomarkers and drug targets for OA.