Sun Yan, Chen Liang-Hong, Lu Yan-Song, Chu Hai-Tao, Wu Yan, Gao Xing-Hua, Chen Hong-Duo
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, China.
Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Cytokine. 2021 May;141:155444. doi: 10.1016/j.cyto.2021.155444. Epub 2021 Jan 30.
Rosacea is a chronic inflammatory skin disease whose psychological consequences severely affect patient's quality of life.
To identify candidate genes of rosacea for potential development of new target therapies.
Gene Expression Omnibus datasets were retrieved to obtain differentially expressed genes (DEGs) between rosacea patients and healthy controls. Gene ontology (GO) analyses were used to identify functions of candidate genes. Related signaling pathways of DEGs were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis. Protein-protein interaction (PPI) networks were applied using search tools for the retrieval of interacting genes/proteins and modulations involving PPI networks were evaluated with use of the MCODE app.
Samples from 19 rosacea patients and 10 healthy controls of dataset GSE65914 were enrolled. A total of 215 DEGs, 115 GO terms and 6 KEGG pathways were identified. A total of 182 nodes and 456 edges were enriched in PPI networks. Maximal clusters showed 15 central nodes and 96 edges. The toll-like receptor (TLR) signaling pathway was the most significant pathway detected and 5 DEGs were identified as candidate genes which included TLR2, C-C motif chemokine (CCL) 5, C-X-C motif chemokine ligand (CXCL) 9, CXCL10 and CXCL11. The results were verified in rosacea patients with use of real-time polymerase chain reaction and immunohistochemistry. Cell-type enrichment analysis revealed 8 lymphocytes that were enriched in rosacea patients.
The results suggest that both innate and adaptive immune responses were involved in the etiology of rosacea. Five DEGs in the TLR signaling pathway may serve as potential therapeutic target genes.
酒渣鼻是一种慢性炎症性皮肤病，其心理影响严重影响患者的生活质量。
鉴定酒渣鼻的候选基因，为新的靶向治疗开发提供潜在依据。
检索基因表达综合数据集，以获取酒渣鼻患者与健康对照之间的差异表达基因（DEG）。利用基因本体（GO）分析来鉴定候选基因的功能。使用京都基因与基因组百科全书（KEGG）和基因集富集分析对DEG的相关信号通路进行分析。应用蛋白质-蛋白质相互作用（PPI）网络，使用搜索工具检索相互作用基因/蛋白质，并使用MCODE应用程序评估涉及PPI网络的调控。
纳入数据集GSE65914中的19例酒渣鼻患者和10例健康对照的样本。共鉴定出215个DEG、115个GO术语和6条KEGG通路。PPI网络中共富集了182个节点和456条边。最大的聚类显示有15个中心节点和96条边。Toll样受体（TLR）信号通路是检测到的最显著通路，5个DEG被鉴定为候选基因，包括TLR2、C-C基序趋化因子（CCL）5、C-X-C基序趋化因子配体（CXCL）9、CXCL10和CXCL11。通过实时聚合酶链反应和免疫组织化学在酒渣鼻患者中验证了结果。细胞类型富集分析显示酒渣鼻患者中有8种淋巴细胞富集。
结果表明，先天性和适应性免疫反应均参与了酒渣鼻的病因。TLR信号通路中的5个DEG可能作为潜在的治疗靶基因。
