Analysis on the expression and clinical significance of MOSPD2 in rheumatoid arthritis based on weighted gene co-expression network / 中华风湿病学杂志

ABSTRACT

Objective:To identify the key genes related to rheumatoid arthritis (RA) by to the weighted gene co-expression network analysis (WGCNA) and experimental verification to find key genes related to RA.Methods:The microarray data of RA were downloaded from the Gene Expression Omnibus (GEO) database. Gene network was constructed, and the genes were classified into different modules using WGCNA. HUB genes in modules related to RA clinical symptoms were analyzed by gene ontology. Subsequently, different data sets of GEO were used to verify the expression profile and diagnostic capacity of the HUB gene [receiver operating characteristic curve (ROC)]. In addition, the expression of HUB gene in RA was verified by real time polymerase chain reaction (RT-PCR) and Western blot, and the relationship between key genes and disease activity score 28 joints (DAS28) was analyzed. Paired-sample t-test and Pearson's correlation analysis was used for statistical analysis. Results:A total of 5 413 differentially expressed genes were filtered. Weighted gene coexpression network was constructed and genes were classified into 23 modules. Among them, the black module is closely related to the clinical symptoms of RA, which contained 346 genes. Enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signal pathway analysis showed that it was to be enriched in the positive regulation of interleukin 6, interleukin 1 beta secretion, osteoclast differentiation, NOD-like receptor signaling pathway, T helper cell 17 (Th17) cell differentiation and many other pathways closely related to RA. Motile sperm domain-containing protein 2 (MOSPD2) was significantly correlated with clinical symptoms. It was highly expressed in blood monocytes and bone marrow monocytes ( t=2.238, P=0.032; t=3.153, P=0.006), and positively correlated with blood expression in RA joint synovial fluid ( r=0.683, P=0.03). ROC curve analysis determined that MOSPD2 could distinguish RA from the control group (the area under the curve was 0.855 and 0.726) respectively. RT-PCR and Western blotting results showed that MOSPD2 was up-regulated in RA patients ( t=-3.96, P=0.02). MOSPD2 expression levels in blood were positively correlated with DAS28 in RA patients ( r=0.884 6, P=0.046 2). Conclusion:MOSDP2 is closely related to the clinical symptoms of RA patients, and may be one of the targets for the diagnosis and treatment of RA.