Comprehensive bioinformatics analysis uncover molecular pathways shared between osteoarthritis and atherosclerosis.

BACKGROUND

There is growing evidence of an association between osteoarthritis (OA) and atherosclerosis (AS). However, their mechanisms are not yet fully understood. The aim of this study was to investigate the common genetic and molecular mechanisms underlying the common pathogenesis of OA and AS.

METHODOLOGY

Gene expression profiles of OA (GSE51588) and AS (GSE100927) were obtained from the Gene Expression Omnibus (GEO) database. After identifying shared differentially expressed genes (DEGs) and hub genes, we performed multifaceted bioinformatics analyses, including functional annotation, co-expression analysis, TF-mRNA and ceRNA regulatory network construction, pharmacogenetic prediction, and receiver operator characteristic (ROC) curve assessment. In addition, the immune infiltration of OA and AS was analyzed and compared based on the ssGSEA algorithm, and the correlation between hub genes and infiltrating immune cells was evaluated in OA and AS, respectively.

RESULT

A total of 48 up-regulated and 43 down-regulated public DEGs were screened between GSE51588 and GSE100927, and functional enrichment analysis emphasized the important role of immune and inflammatory pathways in OA and AS. After protein-protein interaction (PPI) network construction, a total of 9 hub genes (CCR5, IFIT2, MMP1, CXCL9, RSAD2, IFIH1, TNF, IFIT3, and TBX21) were identified as key genes. Targeting the key genes we identified several molecular drug candidates against OA combined with AS related. Additionally diagnostic efficacy assessment using 9 central genes showed great diagnostic value (area under the curve from 0.710 to 0.973). Immune infiltration study also revealed coordinated changes in immune cell profiles in OA and AS diseases.

CONCLUSION

After a series of bioinformatics analysis and validation, CCR5, IFIT2, MMP1, CXCL9, RSAD2, IFIH1, TNF, IFIT3 and TBX21 were identified as common hub genes for the development of OA and AS. This study provides a new perspective on the common molecular mechanisms between OA and AS, and offers new insights into the potential pathogenesis of OA combined with AS and the direction of treatment.