University of Colorado Denver, Colorado School of Public Health, Division of Allergy and Clinical Immunology, Aurora, CO 80045, USA.
Occup Environ Med. 2011 Oct;68(10):759-64. doi: 10.1136/oem.2010.058966. Epub 2011 Jan 27.
People exposed to beryllium may develop beryllium sensitisation (BeS) and, in some cases, progress to chronic beryllium disease (CBD).
The objective of this study was to test the ability of proteomic technology to identify patterns of serum protein biomarkers that allow differentiation between BeS and CBD and thus remove the need for invasive bronchoscopic procedures.
Initially, SELDI-TOF methodology and analysis was performed on serum samples from 30 CBD and 31 BeS patients.
This 'starter set' yielded two distinct biomarker pattern sets with eight candidate proteins. The first set differentiated between BeS and CBD with 83.3% sensitivity and 82.3% specificity, with 10-fold cross-validation of 75% and 79%, respectively. The second set of biomarkers yielded higher sensitivity (90.0%) and higher specificity (90.3%), with 10-fold cross-validation of 71.7% and 82.3%, respectively. Due to its greater sensitivity and specificity, the second set of biomarkers was used as the framework for differentiating between CBD and BeS in a second set of serum samples from 450 patients with BeS and CBD. When this larger set of samples was subjected to the biomarker framework in a blinded fashion, it yielded a sensitivity of 43.53% and a specificity of 38.93%.
Due to these low sensitivity and specificity values, we have concluded that, currently, the unique set of SELDI-TOF derived biomarkers does not possess the qualities that would allow it to differentiate between a CBD patient and a BeS patient using serum protein biomarkers. Future refinements in sample collection or proteomic technology may be needed to improve biomarker discovery.
接触铍的人可能会出现铍敏化（BeS），在某些情况下，还会进展为慢性铍病（CBD）。
本研究旨在测试蛋白质组学技术识别血清蛋白生物标志物模式的能力，这些模式可区分 BeS 和 CBD，从而无需进行有创性支气管镜检查。
最初，采用 SELDI-TOF 方法和分析方法对 30 名 CBD 和 31 名 BeS 患者的血清样本进行了分析。
该“起始集”产生了两个具有八个候选蛋白的截然不同的生物标志物模式集。第一组标志物集可将 BeS 和 CBD 区分开来，敏感性为 83.3%，特异性为 82.3%，10 倍交叉验证的敏感性和特异性分别为 75%和 79%。第二组生物标志物的敏感性（90.0%）和特异性（90.3%）更高，10 倍交叉验证的敏感性和特异性分别为 71.7%和 82.3%。由于其更高的敏感性和特异性，第二组生物标志物被用作区分 450 名 BeS 和 CBD 患者血清样本中 CBD 和 BeS 的框架。当以盲法将这组更大的样本应用于生物标志物框架时，其敏感性为 43.53%，特异性为 38.93%。
由于这些敏感性和特异性值较低，我们得出结论，目前，SELDI-TOF 衍生的生物标志物的独特集不具备使用血清蛋白生物标志物区分 CBD 患者和 BeS 患者的特性。可能需要改进样本收集或蛋白质组学技术以提高生物标志物的发现。
