系统性硬化症伴间质性肺病的潜在标志物和治疗靶点

Potential biomarkers and therapeutic targets for systemic sclerosis with interstitial lung disease

目的通过分析系统性硬化症伴间质性肺病(systemic sclerosis with interstitial lung disease,SSc-ILD)患者与健康对照肺组织基因表达情况,筛选出SSc-ILD的潜在标志物和治疗靶点,并探究其参与SSc-ILD的可能发病机制。方法计算2个芯片(GSE76808、GSE81292)中的差异表达基因(differentially expressed genes,DEGs),取2个芯片共同表达的DEGs,对其进行功能注释、功能富集和蛋白质相互作用网络分析。CTD、GENE和DisGeNET数据库验证SSc-ILD的相关基因。结果2个芯片共同表达的DEGs 230个,其中59个基因表达上调,171个基因表达下调。CTD数据库中与SSc和ILD存在关联的基因10694个;GENE数据库中与SSc和ILD存在关联的基因50个;DisGeNET数据库中与SSc有关的基因980个。结合芯片和3个数据库分析结果,IL-6、CXCL8、CCL2、IL-1B、ICAM1、JUN、PTGS2、TNFAIP3可能是SSc-ILD的潜在标志物和治疗靶点。结论IL-6、CXCL8、CCL2、IL-1B、ICAM1、JUN、PTGS2、TNFAIP3可能参与了SSc-ILD的发病机制,有望作为SSc-ILD的潜在标志物和治疗靶点。

Objective To screen out potential biomarkers and therapeutic targets for systemic sclerosis with interstitial lung disease(SSc-ILD)and explore its possible role in the pathogenesis of SSc-ILD,we analyzed gene expression in lung tissue of patients with SSc-ILD and healthy controls.Methods We calculated and screened out the co-expressed differentially expressed genes(DEGs)in two chips(GSE76808,GSE81292),and performed functional annotation,functional enrichment,and protein interaction network analysis on them.The datebases of CTD,GENE and DisGeNET were used to validate the related genes of SSc-ILD.Results There were 230 co-expressed DEGs in the two chips,of which 59 genes were up-regulated and 171 genes were down-regulated.There were 10694 genes related to SSc and ILD in the CTD database;50 genes related to SSc and ILD in the GENE database;980 genes related to SSc in the DisGeNET database.Combined with the analysis results of the chips and three databases,IL-6,CXCL8,CCL2,IL-1B,ICAM1,JUN,PTGS2,TNFAIP3 might be the potential biomarkers and therapeutic targets of SSc-ILD.Conclusion IL-6,CXCL8,CCL2,IL-1B,ICAM1,JUN,PTGS2,TNFAIP3 might be involved in the pathogenesis of SSc-ILD,which were expected to serve as potential biomarkers and therapeutic targets of SSc-ILD.