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揭示克罗恩病合并银屑病的常见疾病机制和关键生物标志物,并探索潜在治疗药物。

Uncovering common disease mechanisms and critical biomarkers in Crohn's disease with concurrent psoriasis and exploring potential therapeutic agents.

作者信息

Liu Tianqi, Zhang Xiaoqing, Chen Ruiqi, Sun Yifan, Zhang Ruijian, Zhang Liwen, Luo Zhepeng, Wang Jiani

机构信息

Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning Province, China.

Teaching Center for Medical Experiment, China Medical University, Shenyang, Liaoning Province, China.

出版信息

PLoS One. 2025 Jun 20;20(6):e0324007. doi: 10.1371/journal.pone.0324007. eCollection 2025.

Abstract

INTRODUCTION

Research findings show a substantial correlation between Crohn's disease and psoriasis. However, the exact cause or pathogenesis of the concurrent manifestations of these two conditions in the same individuals remains uncertain. This research aimed to scrutinize the important molecules and mechanisms responsible for the concomitance of Crohn's disease and Psoriasis by using quantitative bioinformatics utilizing a publicly available RNA sequencing repository.

METHODS

The database Gene Expression Omnibus were assessed, specifically for Crohn's disease (GSE95095) and psoriasis (GSE13355). The 'limma' library of the R programming syntax is employed to identify differentially expressed genes. The Search Tool for Interacting Genes dataset was utilized to study the interaction between proteins networks. The Cytoscape software was utilized to efficiently view and analyse these Protein-Protein Interaction networks. The ctoHubba Cytoscape plugin helps in the selection of hub genes. These hub genes have been confirmed using data from GSE102133 for Crohn's disease and GSE14905 for psoriasis. The ROC curves were utilized in this study to assess the diagnostic value of the hub genes. Moreover, new research involving gene-set enriched studies and the study of immunological surveillance associated with these specific genes is attainable.

RESULTS

Among the identified common DEGs, 40 genes were downregulated and 37 were upregulated, totaling 77 genes. Crohn's disease and Psoriasis had a higher concentration of pathways associated with inflammation. After validation, functionality of hub genes was confirmed for S100A12, CXCL8, IL1RN, S100A9, CXCL10, MMP1, CXCL1, FPR1, CXCR2, and S100A8. The hub genes showed an increase in expression in response to neutrophil infiltration. The expression of S100A12, CXCL8, IL1RN, S100A9, CXCL10, MMP1, CXCL1, FPR1, CXCR2, and S100A8 was found to be significantly linked to immune processes such as neutrophil activation, neutrophil chemotaxis, and neutrophil migration associated with Crohn's and Psoriasis disease.

CONCLUSIONS

This bioinformatics study has elucidated S100A12, CXCL8, IL1RN, S100A9, CXCL10, MMP1, CXCL1, FPR1, CXCR2, and S100A8 as the central genes in the pathogenesis of CD and Psoriasis comorbidity. The significance of neutrophil infiltration in promoting inflammatory and immune-mediated dysfunction seems to be crucial in the etiology of concurrent Crohn's and Psoriasis, offering an avenue for diagnostic and therapeutic methods.

摘要

引言

研究结果表明克罗恩病与银屑病之间存在显著相关性。然而,这两种疾病在同一患者中并发表现的确切原因或发病机制仍不明确。本研究旨在通过利用公开可用的RNA测序数据库进行定量生物信息学分析,仔细研究导致克罗恩病和银屑病并发的重要分子和机制。

方法

对基因表达综合数据库进行评估,特别是针对克罗恩病(GSE95095)和银屑病(GSE13355)。使用R编程语言语法的“limma”库来识别差异表达基因。利用相互作用基因搜索工具数据集研究蛋白质网络之间的相互作用。使用Cytoscape软件有效查看和分析这些蛋白质-蛋白质相互作用网络。ctoHubba Cytoscape插件有助于选择枢纽基因。这些枢纽基因已使用来自克罗恩病的GSE102133和银屑病的GSE14905的数据进行了验证。本研究中使用ROC曲线评估枢纽基因的诊断价值。此外,还可进行涉及基因集富集研究以及与这些特定基因相关的免疫监视研究的新研究。

结果

在鉴定出的常见差异表达基因中,40个基因下调,37个基因上调,共计77个基因。克罗恩病和银屑病具有更高浓度的与炎症相关的通路浓度。经过验证,确认了枢纽基因S100A12、CXCL8、IL1RN、S100A9、CXCL10、MMP1、CXCL1、FPR1、CXCR2和S100A8的功能。枢纽基因显示出随着中性粒细胞浸润表达增加。发现S100A12、CXCL8、IL1RN、S100A9、CXCL10、MMP1、CXCL1、FPR1、CXCR2和S100A8的表达与克罗恩病和银屑病相关的免疫过程如中性粒细胞活化、中性粒细胞趋化和中性粒细胞迁移显著相关。

结论

这项生物信息学研究阐明了S100A12、CXCL8、IL1RN、S100A9、CXCL10,、MMP1、CXCL1、FPR1、CXCR2和S100A8是克罗恩病和银屑病合并症发病机制中的核心基因。中性粒细胞浸润在促进炎症和免疫介导功能障碍方面的重要性在克罗恩病和银屑病并发的病因学中似乎至关重要,为诊断和治疗方法提供了一条途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d661/12180644/4402bfdbe71d/pone.0324007.g001.jpg

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