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基于基因表达分析:治疗银屑病的 Guselkumab 快速应答者的特征是低密度中性粒细胞表达。

Based on Gene Expression Analysis: Low-Density Neutrophil Expression Is a Characteristic of the Fast Responders Treated With Guselkumab for Psoriasis.

机构信息

Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.

Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.

出版信息

Front Immunol. 2022 May 26;13:865875. doi: 10.3389/fimmu.2022.865875. eCollection 2022.

Abstract

Psoriasis is a worldwide chronic inflammatory skin disease. The treatment of disease is usually designed according to its severity. In this research, RNA-seq was performed on 37 patients with psoriasis treated with guselkumab before and after treatment, and the patients were divided into fast responder and slow responder according to PASI score to analyze the differentially expressed genes (DEGs) between them. Moreover, The biological mechanism of psoriasis was explored by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Ontology (GO) analysis, and Gene Set Enrichment Analysis (GSEA) analysis. And then, this protein-protein interaction network was constructed and 17 DEGs including IL-1β, CXCL8, S100A12 and MMP9 were analyzed by GSVA. DEGs were detected by GO and KEGG analysis of target genes, which were primarily associated with immune response, neutrophil activation, neutrophil degranulation. GSEA reminded that fast responders were mainly involved in low-density neutrophils and abundant NK cells. And the GSVA showed that the DEGs were down-regulated after the early stage of the fast responder and the reverse in the slow responder by GSVA analysis. On the whole, these results indicated that these DEGs may serve as a psoriasis potential diagnostic and predictive biomarkers after been treated by guselkumab.

摘要

银屑病是一种全球性的慢性炎症性皮肤病。疾病的治疗通常根据其严重程度设计。在这项研究中,对 37 名接受古塞单抗治疗的银屑病患者进行了 RNA-seq 检测,根据 PASI 评分将患者分为快速应答者和缓慢应答者,以分析他们之间的差异表达基因(DEGs)。此外,通过京都基因与基因组百科全书(KEGG)分析、基因本体论(GO)分析和基因集富集分析(GSEA)分析探讨了银屑病的生物学机制。然后,构建了这个蛋白质-蛋白质相互作用网络,并通过 GSVA 分析了包括 IL-1β、CXCL8、S100A12 和 MMP9 在内的 17 个 DEGs。通过对靶基因的 GO 和 KEGG 分析检测到 DEGs,这些基因主要与免疫反应、中性粒细胞活化、中性粒细胞脱颗粒有关。GSEA 提醒快速应答者主要涉及低浓度中性粒细胞和丰富的 NK 细胞。通过 GSVA 分析显示,快速应答者在早期阶段这些 DEGs 下调,而在缓慢应答者中则相反。总的来说,这些结果表明,这些 DEGs 可能成为古塞单抗治疗后银屑病潜在的诊断和预测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdf0/9177995/57be3ee43de7/fimmu-13-865875-g001.jpg

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