School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, Australia.
Am J Respir Crit Care Med. 2011 Jun 15;183(12):1633-43. doi: 10.1164/rccm.201010-1623OC. Epub 2011 Mar 18.
Proteomics may identify a useful panel of biomarkers for identification of asthma and chronic obstructive pulmonary disease (COPD).
To conduct an unsupervised analysis of peripheral blood proteins in well-characterized subjects with asthma and COPD, and identify and validate a biomarker panel for disease discrimination.
Two-dimensional difference gel electrophoresis was used to separate plasma proteins from healthy control subjects, stable patients with asthma, and individuals with COPD. Candidate protein markers were identified by matrix assisted laser desorption ionization time of flight mass spectrometry and subsequently validated in two populations via immunoassay. A panel of four biomarkers was selected and their ability to distinguish between groups was assessed in isolation and in combination in two separate validation populations.
Seventy-two protein spots displayed significantly different expression levels between the three subject groupings (P < 0.05). Fifty-eight were positively identified, representing 20 unique proteins. A panel of four biomarkers (α(2)-macroglobulin, haptoglobin, ceruloplasmin, and hemopexin) was able to discriminate with statistical significance between the clinical groups of patients with asthma, patients with COPD, and control subjects, and these results were confirmed in a second clinical population of older adults with airflow obstruction.
Proteomics has identified novel biomarkers for asthma and COPD, and shown that the iron metabolism pathways and acute-phase response may be involved in the pathogenesis of airway disease. The panel of peripheral blood biomarkers has the potential to become an extremely useful addition to the clinical diagnosis and management of respiratory disease.
蛋白质组学可能会识别出用于鉴定哮喘和慢性阻塞性肺疾病（COPD）的有用生物标志物组。
对特征明确的哮喘和 COPD 患者的外周血蛋白进行非监督分析，并确定和验证用于疾病区分的生物标志物组。
使用二维差异凝胶电泳技术分离健康对照者、稳定期哮喘患者和 COPD 患者的血浆蛋白。通过基质辅助激光解吸电离飞行时间质谱鉴定候选蛋白标志物，并通过免疫测定在两个群体中进一步验证。选择一个由四个生物标志物组成的小组，并评估其在两个单独的验证群体中单独和组合区分组别的能力。
72 个蛋白斑点在三组受试者之间显示出明显不同的表达水平（P < 0.05）。其中 58 个被阳性鉴定，代表 20 个独特的蛋白质。一个由四个生物标志物（α（2）-巨球蛋白、触珠蛋白、铜蓝蛋白和血红素结合蛋白）组成的小组能够在哮喘、COPD 患者和对照组之间进行统计学上的区分，这些结果在另一个具有气流阻塞的老年成人临床群体中得到了证实。
蛋白质组学已经鉴定出用于哮喘和 COPD 的新型生物标志物，并表明铁代谢途径和急性期反应可能参与了气道疾病的发病机制。该外周血生物标志物组有可能成为呼吸疾病临床诊断和管理的极有价值的补充。
