通过转录组学鉴定慢性阻塞性肺疾病中与线粒体功能障碍和程序性细胞死亡相关的生物标志物

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY

Frontiers in Genetics Pub Date : 2025-06-19 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1567173

Xiaojuan Yang, Yutao Duan, Lei Qiu, Xia Huang, Fei Li

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引用次数: 0

摘要

背景：研究表明，线粒体稳态和程序性细胞死亡（PCD）与慢性阻塞性肺疾病（COPD）密切相关。因此，从线粒体相关基因（MRGs）和程序性细胞死亡相关基因（PCD-RGs）中鉴定COPD的生物标志物至关重要。方法：通过加权基因共表达网络分析（WGCNA）将GSE42057数据集中的差异表达基因（deg）和copd相关基因（COPD-RGs）与mrg和PCD-RGs交叉筛选候选基因。机器学习识别了生物标志物，并在GSE42057和GSE94916数据集上进行了验证。途径富集、免疫浸润和药物预测分析。结果：从交叉的DEGs、COPD-RGs、MRGs和PCD-RGs中获得8个候选基因。5种生物标志物（BCL2、CCR7、FAM162A、fox01、RPS3）在COPD中表现出一致的失调。这些生物标志物激活了“核糖体”途径。CCR7、FOXO1与naïve B细胞呈正相关，BCL2与M0巨噬细胞负相关。BCL2与dolastatin 10、beauvericin和胶束紫杉醇有很强的结合。RT-qPCR证实生物标志物表达。结论：BCL2、CCR7、FAM162A、FOXO1、RPS3是COPD的生物标志物，为COPD的治疗提供了新的突破点。

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Identification of biomarkers associated with mitochondrial dysfunction and programmed cell death in chronic obstructive pulmonary disease via transcriptomics.

Background: Research has demonstrated that the homeostasis of mitochondria and programmed cell death (PCD) are intimately linked to chronic obstructive pulmonary disease (COPD). Consequently, identifying biomarkers of COPD from mitochondria-related genes (MRGs) and programmed cell death-related genes (PCD-RGs) is of paramount importance.

Methods: Differentially expressed genes (DEGs) from the GSE42057 dataset and COPD-related genes (COPD-RGs) via weighted gene co-expression network analysis (WGCNA) were intersected with MRGs and PCD-RGs to select candidates. Machine learning identified biomarkers, validated across GSE42057 and GSE94916 datasets. Pathway enrichment, immune infiltration, and drug prediction analyses were performed.

Results: Eight candidate genes were derived from intersecting DEGs, COPD-RGs, MRGs, and PCD-RGs. Five biomarkers (BCL2, CCR7, FAM162A, FOXO1, RPS3) were identified, showing consistent dysregulation in COPD. These biomarkers activated the "ribosome" pathway. CCR7 and FOXO1 correlated positively with naïve B cells, while BCL2 negatively correlated with M0 macrophages. BCL2 exhibited strong binding to dolastatin 10, beauvericin, and micellar paclitaxel. RT-qPCR confirmed biomarker expression.

Conclusion: BCL2, CCR7, FAM162A, FOXO1, and RPS3 are biomarkers for COPD, providing a new breakthrough point for the treatment of this disease.

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来源期刊

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.