蛋白质组学和代谢组学分析揭示了稳定期 COPD 患者循环诊断生物标志物和分子亚型的特征。
Proteomics and metabolomics profiling reveal panels of circulating diagnostic biomarkers and molecular subtypes in stable COPD.
机构信息
State Key Laboratory of Respiratory Diseases, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Guangzhou Laboratory, Guangzhou, 510005, Guangdong, China.
出版信息
Respir Res. 2023 Mar 11;24(1):73. doi: 10.1186/s12931-023-02349-x.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease with high morbidity and mortality, especially in advanced patients. We aimed to develop multi-omics panels of biomarkers for the diagnosis and explore its molecular subtypes.
METHODS
A total of 40 stable patients with advanced COPD and 40 controls were enrolled in the study. Proteomics and metabolomics techniques were applied to identify potential biomarkers. An additional 29 COPD and 31 controls were enrolled for validation of the obtained proteomic signatures. Information on demographic, clinical manifestation, and blood test were collected. The ROC analyses were carried out to evaluate the diagnostic performance, and experimentally validated the final biomarkers on mild-to-moderate COPD. Next, molecular subtyping was performed using proteomics data.
RESULTS
Theophylline, palmitoylethanolamide, hypoxanthine, and cadherin 5 (CDH5) could effectively diagnose advanced COPD with high accuracy (auROC = 0.98, sensitivity of 0.94, and specificity of 0.95). The performance of the diagnostic panel was superior to that of other single/combined results and blood tests. Proteome based stratification of COPD revealed three subtypes (I-III) related to different clinical outcomes and molecular feature: simplex COPD, COPD co-existing with bronchiectasis, and COPD largely co-existing with metabolic syndrome, respectively. Two discriminant models were established using the auROC of 0.96 (Principal Component Analysis, PCA) and 0.95 (the combination of RRM1 + SUPV3L1 + KRT78) in differentiating COPD and COPD with co-morbidities. Theophylline and CDH5 were exclusively elevated in advanced COPD but not in its mild form.
CONCLUSIONS
This integrative multi-omics analysis provides a more comprehensive understanding of the molecular landscape of advanced COPD, which may suggest molecular targets for specialized therapy.
背景
慢性阻塞性肺疾病（COPD）是一种复杂且异质性的疾病，发病率和死亡率都很高，尤其是在晚期患者中。我们旨在开发用于诊断的多组学生物标志物面板，并探索其分子亚型。
方法
本研究共纳入 40 例晚期 COPD 稳定期患者和 40 名对照者。应用蛋白质组学和代谢组学技术来鉴定潜在的生物标志物。另外还纳入了 29 例 COPD 和 31 例对照者来验证获得的蛋白质组学特征。收集了人口统计学、临床表现和血液检查的信息。进行了 ROC 分析以评估诊断性能，并在轻度至中度 COPD 患者中对最终的生物标志物进行了实验验证。然后，使用蛋白质组学数据进行分子亚型分析。
结果
茶碱、棕榈酸乙醇酰胺、次黄嘌呤和钙黏蛋白 5（CDH5）可以有效地诊断晚期 COPD，准确性高（auROC=0.98，敏感性为 0.94，特异性为 0.95）。该诊断面板的性能优于其他单一/联合结果和血液检查。基于蛋白质组的 COPD 分层揭示了三种与不同临床结局和分子特征相关的亚型（I-III）：单纯 COPD、同时存在支气管扩张的 COPD 以及主要与代谢综合征共存的 COPD。使用 auROC 为 0.96（主成分分析，PCA）和 0.95（RRM1+SUPV3L1+KRT78 的组合）的两个判别模型建立了区分 COPD 和合并症的 COPD 的模型。茶碱和 CDH5 仅在晚期 COPD 中升高，而在轻度 COPD 中不升高。
结论
这项综合多组学生物分析提供了对晚期 COPD 分子特征的更全面的理解，这可能为特异性治疗提供了分子靶点。
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