Yang Yang, Xie Shaoqiong, Jiang Wencheng, Tang Suwei, Shi Yuling
Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, People's Republic of China.
Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, 200092, People's Republic of China.
Int J Gen Med. 2022 Mar 11;15:2817-2833. doi: 10.2147/IJGM.S354985. eCollection 2022.
This study aimed to investigate key biomarkers and their molecular pathogenesis in psoriasis.
Differentially expressed genes (DEGs) of datasets (GSE13355, GSE30999, and GSE106992) obtained from Gene Expression Omnibus (GEO) were identified using Venn diagram. Function and pathway enrichment analyses were performed. Protein-protein interaction (PPI) network and the hub genes were constructed. The correlation between normal tissue and infiltrating immune cells was analyzed by CIBERSORT. ROC analysis was performed to distinguish between skin lesion samples and skin non-lesion samples. Analyze the highest expression of single gene in the whole body within the Human Protein Atlas (HPA) database. Effect of CXCL8 expression level on proliferation, invasion, migration and apoptosis of HaCat cells was detected by qPCR.
A total of 239 pairs of normal and lesional skin samples were downloaded. PPI network revealed a tight interaction among 197 DEGs. The GO enrichment analysis showed that these genes were markedly enriched in the "defense response to virus", "type I interferon signaling pathway", and "cell response to type I interferon" categories. The KEGG pathway analysis showed that the DEGs were mainly in the NOD-like receptor axis, interaction between cytokine and cytokine receptor and the IL-17 axis. PPI analysis showed that CXCL8 was the novel hub gene of psoriasis and correlated to 22 types of infiltrating immune cells. 6 miRNAs were predicted to be related to CXCL8. CXCL8 was most widely distributed in lymphoid tissues and plays a role in psoriatic inflammatory lesions by promoting cell proliferation, migration, and anti-apoptosis.
CXCL8 plays a key role in psoriasis development. This study provided new insights into the exploration of molecular mechanisms and therapeutic targets of psoriasis.
本研究旨在探究银屑病的关键生物标志物及其分子发病机制。
使用韦恩图鉴定从基因表达综合数据库（GEO）获得的数据集（GSE13355、GSE30999和GSE106992）中的差异表达基因（DEG）。进行功能和通路富集分析。构建蛋白质-蛋白质相互作用（PPI）网络和枢纽基因。通过CIBERSORT分析正常组织与浸润免疫细胞之间的相关性。进行ROC分析以区分皮肤病变样本和皮肤非病变样本。在人类蛋白质图谱（HPA）数据库中分析单个基因在全身的最高表达。通过qPCR检测CXCL8表达水平对HaCaT细胞增殖、侵袭、迁移和凋亡的影响。
共下载了239对正常和病变皮肤样本。PPI网络显示197个DEG之间存在紧密相互作用。GO富集分析表明，这些基因在“对病毒的防御反应”、“I型干扰素信号通路”和“对I型干扰素的细胞反应”类别中显著富集。KEGG通路分析表明，DEG主要存在于NOD样受体轴、细胞因子与细胞因子受体相互作用以及IL-17轴中。PPI分析表明，CXCL8是银屑病的新型枢纽基因，与22种浸润免疫细胞相关。预测有6种miRNA与CXCL8相关。CXCL8在淋巴组织中分布最广泛，通过促进细胞增殖、迁移和抗凋亡在银屑病炎症病变中发挥作用。
CXCL8在银屑病发展中起关键作用。本研究为银屑病分子机制和治疗靶点的探索提供了新见解。
