Specific Gene Expression and Small-Molecule Drug Investigation in Ankylosing Spondylitis under Interferon-γ Stimulation

摘要

Background and Objective: Interferon (IFN)-γ plays crucial roles in the development of ankylosing spondylitis (AS) though regulating its sensitive response genes, but the sensitive response genes to IFN-γ dysregulation in AS are partially reported. Thus, the present study explored potential target genes for AS treatment under interferon-γ (IFN-γ) stimulated condition. Materials and Methods: The gene expression profile, GSE11886 was downloaded. The differentially expressed genes (DEGs) in non-INF-γ group and INF-γ group were revealed respectively, followed by function and pathway enrichment analyses, as well as protein-protein interaction network analysis. Furthermore, the small-molecule drugs associated with AS were identified. Finally, the data validation for DEGs in AS with non-INF-γ interference was conducted using another dataset GSE25101. Results: Totally, 317 DEGs and 394 DEGs were revealed in the INF-γ group and non-INF-γ group, respectively. Venn diagram revealed 60 overlapped DEGs. Among the 394 DEGs, nineteen genes were verified in non-INF-γ group. The DEGs in the two groups were mainly enriched in mitotic cell cycle and T cell activation, respectively. CKD1 and BUB1 were outstanding in INF-γ group, while the validated PRKCQ and SMARCA4 might be crucial with AS in non-INF-γ group. In addition, the DL-thiorphan and NS-398 had the highest negative correlation with DEGs in two groups, respectively. Conclusion: Genes like CDK1 and BUB1 might be novel INF-γ sensitive response gene for AS. The PRKCQ and SMARCA might be strongly related to the process of AS. In addition, NS-398 and DL-thiorphan might be ideal small-molecule drugs for AS treatment.