Screening potential biomarkers of osteoarthritis based on integrated bioinformatics / 中华创伤骨科杂志

ABSTRACT

Objective:To screen the potential characteristic gene spectrums and signal pathways of osteoarthritis based on gene chips.Methods:We analyzed 2 microarrays of human joint synovial tissue (GSE82107 and GSE55235) derived from the Gene Expression Omnibus (GEO) database and included for this study 20 osteoarthritis (OA) samples and 17 healthy control samples. The differentially expressed genes (DEGs) between OA and HC were screened by GEO2R tool. Analyses of Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were performed using the Database for Annotation, Visualization and Integrated Discovery to identify the pathways and functional annotations of DEGs (https//david.ncifcrf.gov/). Protein-protein interaction of these DEGs was analyzed based on the Search Tool for the Retrieval of Interacting Genes database and visualized by Cytoscape software (http//www.string-db.org/).Results:191 up-regulated DEGs and 49 down-regulated DEGs were screened out from the 2 microarray databases. Enrichment of DEGs was mainly found in regulation of such biological functions as "inflammation" , "bone cell differentiation" and "positive apoptotic cell regulation" , HTLV-I infection, silk crack on the original amp-activated protein kinase (MAPK) signaling pathway, swine flu, tumor necrosis factor (TNF) signaling pathway, the nf-kappa B signaling pathway, PI3 kinase/Akt pathway, toll-like receptor pathway, legionella, salmonella and other 14 signaling pathways. In 2 modes of MNC and Degree, the top 10 core genes were screened, of which interleukin-6 (IL6), JUN, chemokine 8 (CXCL8), early reaction growth factor (EGR1) and cyclin (CCND1) were identified as valuable biomarkers of OA.Conclusions:Based on GEO chips, 10 characteristic gene profiles such as IL6, JUN, CXCL8, EGR1, CCND and 14 signal pathways such as tumor necrosis factor (TNF) signal pathway, NF-κB signal pathway, PI3 kinase/Akt pathway and Toll-like receptor pathway were screened, which may provide new clues for understanding of the pathogenesis of osteoarthritis.