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多组学整合与机器学习识别并验证鼻息肉慢性鼻窦炎中与中性粒细胞胞外诱捕网相关的基因特征。

Multi-omics integration and machine learning identify and validate neutrophil extracellular trap-associated gene signatures in chronic rhinosinusitis with nasal polyps.

作者信息

Shu Fu, Wang Yaping, Li Linglong, Shi Lei, Zhang Feng, Ma Zhixuan, Mao Dehong

机构信息

College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400000, People's Republic of China.

Department of Otorhinolaryngology, Yongchuan Chinese Medicine Hospital Affiliated to Chongqing Medical University, Chongqing 400000, People's Republic of China.

出版信息

Clin Immunol. 2025 Jun;275:110473. doi: 10.1016/j.clim.2025.110473. Epub 2025 Mar 13.

DOI:10.1016/j.clim.2025.110473
PMID:40089249
Abstract

This study aimed to explore the molecular characteristics of neutrophil extracellular traps (NETs) in chronic rhinosinusitis with nasal polyps (CRSwNP). Differentially expressed gene analysis, weighted gene co-expression network analysis, and machine learning algorithms identified three core NETs-associated genes: CXCR4, CYBB, and PTAFR, which were significantly upregulated in CRSwNP patients. The diagnostic performance of these genes was evaluated using receiver operating characteristic (ROC) curves, and their clinical relevance was validated using multicenter data. Immune infiltration analysis showed strong correlations between these genes and neutrophil and immune cell infiltration. Single-cell RNA sequencing demonstrated that these genes were predominantly expressed in myeloid and immune cells and exhibited dynamic changes during disease progression. These genes may contribute to CRSwNP pathogenesis through IL-17 signaling and metabolism-related pathways. This study identifies novel biomarkers and therapeutic targets for precise diagnosis and personalized treatment of CRSwNP.

摘要

本研究旨在探讨伴鼻息肉的慢性鼻-鼻窦炎(CRSwNP)中中性粒细胞胞外陷阱(NETs)的分子特征。差异表达基因分析、加权基因共表达网络分析和机器学习算法确定了三个与NETs相关的核心基因:CXCR4、CYBB和PTAFR,这些基因在CRSwNP患者中显著上调。使用受试者工作特征(ROC)曲线评估这些基因的诊断性能,并使用多中心数据验证其临床相关性。免疫浸润分析显示这些基因与中性粒细胞和免疫细胞浸润之间存在强相关性。单细胞RNA测序表明,这些基因主要在髓系和免疫细胞中表达,并在疾病进展过程中表现出动态变化。这些基因可能通过IL-17信号通路和代谢相关途径促进CRSwNP的发病机制。本研究确定了用于CRSwNP精确诊断和个性化治疗的新型生物标志物和治疗靶点。

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