To explore disease-driving genes and biological pathways in CSU.
Two microarray data sets, e.g., GSE57178 and GSE72540, with mRNA information of skin from CSU patients, were downloaded from the Gene Expression Omnibus (GEO) database. An integrated bioinformatics pipeline including identification of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, co-expression and drug prediction analysis, and immune and stromal cells deconvolution analyses were applied to identify hub genes and key drivers of CSU pathogenesis.
In total, we identified 92 up-regulated and 7 down-regulated genes in CSU lesions. These were significantly enriched in CSU-related pathways such as TNF, NF-κB, and JAK-STAT signaling. Based on PPI network modeling, four genes, i.e., IL-6, TLR-4, ICAM-1, and PTGS-2, were computationally identified as key pathogenic players in CSU. Immune infiltration analyses indicated that dendritic cells, Th2 cells, mast cells, megakaryocyte-erythroid progenitor, preadipocytes, and M1 macrophages were increased in lesional CSU skin.
Our results offer new insights on the pathogenesis of CSU and suggest that TNF, NF-κB, JAK-STAT, IL-6, TLR-4, ICAM-1, and PTGS-2 may be candidate targets for novel CSU treatments.
■探索CSU中的疾病驱动基因和生物学途径。
■两个微阵列数据集,例如,GSE57178和GSE72540,具有CSU患者皮肤的mRNA信息,从基因表达综合(GEO)数据库下载。整合的生物信息学管道,包括差异表达基因(DEGs)的鉴定,功能富集分析,蛋白质-蛋白质相互作用(PPI)网络分析,共表达和药物预测分析,免疫和基质细胞去卷积分析用于确定中心基因和CSU发病机制的关键驱动因素。
■总共,我们在CSU病变中鉴定出92个上调基因和7个下调基因.这些在CSU相关通路如TNF、NF-κB,和JAK-STAT信号。基于PPI网络建模,四个基因,即,IL-6,TLR-4,ICAM-1和PTGS-2被计算确定为CSU的关键致病因子。免疫浸润分析表明树突状细胞,Th2细胞,肥大细胞,巨核细胞-红系祖细胞,前脂肪细胞,CSU病变皮肤中M1巨噬细胞增多。
■我们的结果为CSU的发病机制提供了新的见解,并表明TNF,NF-κB,JAK-STAT,IL-6、TLR-4、ICAM-1和PTGS-2可能是新型CSU治疗的候选靶标。