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机器学习驱动发现TRIM基因作为特发性肺纤维化的诊断生物标志物

Machine Learning-Driven Discovery of TRIM Genes as Diagnostic Biomarkers for Idiopathic Pulmonary Fibrosis.

作者信息

Huang Xiangfei, Yu Wen, Hua Fuzhou, Wei Aiping, Wang Xifeng, Chen Shibiao

机构信息

Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

出版信息

Med Sci Monit. 2025 Jun 20;31:e948510. doi: 10.12659/MSM.948510.

Abstract

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited effective treatments and significant challenges in early diagnosis. Identifying reliable biomarkers is crucial for improving diagnostic accuracy and patient outcomes. MATERIAL AND METHODS We analyzed TRIM family gene expression in IPF patients and healthy controls using GSE93606, GSE33566, and GSE38958 datasets. Consensus clustering and WGCNA identified IPF subtypes and hub genes. Machine learning models (RF, GLM, SVM, XGB) were built to identify key disease genes. A nomogram for clinical prediction was developed and validated. Peripheral blood samples from IPF patients and healthy controls were used to validate gene expression via qPCR. RESULTS TRIM family genes were significantly differentially expressed between IPF patients and healthy controls. Two distinct IPF subtypes (C1 and C2) were identified, each exhibiting unique biological functions and signaling pathways. The RF model outperformed other machine learning models, identifying TNIK, NCL, ROPN1L, MTR, and HNRNPH1 as key disease-characteristic genes. The nomogram demonstrated good predictive accuracy (AUC: 0.741, 95% CI: 0.556-0.897). qPCR validation confirmed increased expression of 4 genes in IPF patients, except for ROPN1L, which showed decreased expression. CONCLUSIONS This study identifies and validates TRIM family genes as potential biomarkers for IPF diagnosis using clinical samples. The findings support the integration of these biomarkers into diagnostic workflows, potentially enhancing early diagnosis and personalized treatment strategies for IPF patients. Further research is needed to explore the prognostic value and underlying mechanisms of these genes.

摘要

背景

特发性肺纤维化(IPF)是一种进行性肺部疾病,有效治疗方法有限,早期诊断面临重大挑战。识别可靠的生物标志物对于提高诊断准确性和患者预后至关重要。

材料与方法

我们使用GSE93606、GSE33566和GSE38958数据集分析了IPF患者和健康对照中TRIM家族基因的表达。共识聚类和加权基因共表达网络分析(WGCNA)确定了IPF亚型和核心基因。构建机器学习模型(随机森林、广义线性模型、支持向量机、极端梯度提升)以识别关键疾病基因。开发并验证了用于临床预测的列线图。使用IPF患者和健康对照的外周血样本通过定量聚合酶链反应(qPCR)验证基因表达。

结果

IPF患者和健康对照之间TRIM家族基因存在显著差异表达。确定了两种不同的IPF亚型(C1和C2),每种亚型都表现出独特的生物学功能和信号通路。随机森林模型优于其他机器学习模型,确定TNIK、NCL、ROPN1L、MTR和HNRNPH1为关键疾病特征基因。列线图显示出良好的预测准确性(曲线下面积:0.741,95%置信区间:0.556 - 0.897)。qPCR验证证实IPF患者中4个基因的表达增加,但ROPN1L除外,其表达降低。

结论

本研究识别并验证了TRIM家族基因作为使用临床样本进行IPF诊断的潜在生物标志物。这些发现支持将这些生物标志物整合到诊断工作流程中,可能增强IPF患者的早期诊断和个性化治疗策略。需要进一步研究来探索这些基因的预后价值和潜在机制。

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