Integrated Analysis of Ferroptosis and Immune Infiltration in Ulcerative Colitis Based on Bioinformatics.

IF 4.2 2区 医学 Q2 IMMUNOLOGY
Journal of Inflammation Research Pub Date : 2025-03-10 eCollection Date: 2025-01-01 DOI:10.2147/JIR.S501651
Daxing Cai, Weitao Hu, Yanliang Cai, Taiyong Fang, Xiaoqing Chen
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引用次数: 0

Abstract

Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease influenced by genetic, immune, and environmental factors. This study investigates the link between ferroptosis, a cell death process related to oxidative stress and iron metabolism, and immune infiltration in UC.

Materials and methods: We analyzed UC patient transcription data from the Gene Expression Omnibus (GEO) and identified ferroptosis-related genes using FerrDB. Using STRING and Cytoscape, we analyzed protein-protein interactions to identify hub UC Differentially Expressed Genes (UCDEGs) and performed functional enrichment with GO and KEGG pathways. Machine learning helped further identify key UC Differentially Expressed Ferroptosis-related genes (UCDE-FRGs), which were validated using additional GEO datasets and immunohistochemical staining.

Results: A total of 11 hub UCDEGs (CCL2, ICAM1, TLR2, CXCL9, MMP9, CXCL10, IL1B, CXCL8, PTPRC, FCGR3A, and IL1A) and 3 key UCDE-FRGs (DUOX2, LCN2 and IDO1) were identified. GO and KEGG functional enrichment indicates that these genes play a role in immunity and ferroptosis. Analysis of immune cell infiltration showed that there were a large number of Plasma cells, Monocytes, M0/M1 Macrophages and Neutrophils in the UC. Correlation analysis revealed 3 key UCDE-FRGs associated with immune-infiltrated cells in UC. IHC results showed that the expression levels of 3 key UCDE-FRGs in UC were all higher than that in the healthy controls.

Conclusion: In summary, this study identified three key genes related to UC ferroptosis and immunity, namely DUOX2, IDO1 and LCN2. These findings suggest that immune infiltration plays an important role in UC caused by ferroptosis, and that there is mutual regulation between UC and immune-infiltrated cells. Our research revealed the potential application of immune and ferroptosis in the diagnosis, treatment and prognosis of UC, providing new strategies for clinical management.

基于生物信息学的溃疡性结肠炎铁下垂与免疫浸润的综合分析。
溃疡性结肠炎(UC)是一种受遗传、免疫和环境因素影响的炎症性肠病。本研究探讨了UC中与氧化应激和铁代谢相关的细胞死亡过程铁凋亡与免疫浸润之间的联系。材料和方法:我们分析了来自Gene Expression Omnibus (GEO)的UC患者转录数据,并使用FerrDB鉴定了铁中毒相关基因。利用STRING和Cytoscape,我们分析了蛋白相互作用,以鉴定中心UC差异表达基因(UCDEGs),并通过GO和KEGG途径进行功能富集。机器学习有助于进一步识别关键的UC差异表达铁凋亡相关基因(UCDE-FRGs),并使用额外的GEO数据集和免疫组织化学染色对其进行验证。结果:共鉴定出11个枢纽UCDEGs (CCL2、ICAM1、TLR2、CXCL9、MMP9、CXCL10、IL1B、CXCL8、PTPRC、FCGR3A和IL1A)和3个关键UCDE-FRGs (DUOX2、LCN2和IDO1)。GO和KEGG功能富集表明这些基因在免疫和铁下垂中发挥作用。免疫细胞浸润分析显示UC内有大量浆细胞、单核细胞、M0/M1巨噬细胞和中性粒细胞。相关性分析显示3个关键UCDE-FRGs与UC中免疫浸润细胞相关。免疫组化结果显示,UC中3个关键UCDE-FRGs的表达水平均高于健康对照组。结论:综上所述,本研究确定了UC铁亡与免疫相关的三个关键基因,分别是DUOX2、IDO1和LCN2。提示免疫浸润在铁下垂性UC中起重要作用,UC与免疫浸润细胞之间存在相互调节作用。我们的研究揭示了免疫和铁下垂在UC的诊断、治疗和预后中的潜在应用,为临床治疗提供了新的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Inflammation Research
Journal of Inflammation Research Immunology and Microbiology-Immunology
CiteScore
6.10
自引率
2.20%
发文量
658
审稿时长
16 weeks
期刊介绍: An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.
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