National Research Centre for Asbestos Related Disease, Sir Charles Gairdner Hospital, 2School of Medicine and Pharmacology, University of Western Australia, QEII Medical Centre, Nedlands, Western Australia, Australia.
Cancer Epidemiol Biomarkers Prev. 2010 Sep;19(9):2238-46. doi: 10.1158/1055-9965.EPI-10-0346. Epub 2010 Jul 22.
Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, primarily caused by exposure to asbestos. Since the recent discovery that serum mesothelin is a sensitive and highly specific biomarker for mesothelioma, one of the key issues raised is whether mesothelin levels represent a useful screening test for asbestos-exposed at-risk individuals. In this study, soluble mesothelin was determined in sequential serum samples collected from asbestos-exposed individuals before the development of mesothelioma.
Archival serum samples from 106 individuals who developed mesothelioma, 99 asbestos-exposed individuals from the Wittenoom Cancer Surveillance Program, and 109 non-asbestos-exposed individuals from the Busselton Health Survey were identified. Serum mesothelin concentrations were determined using the MESOMARK assay.
Longitudinal mesothelin levels determined in healthy asbestos-exposed individuals over a period of 4 years were stable (Pearson's r = 0.96; P < 0.0001). There was no correlation between mesothelin concentration and cumulative asbestos exposure. Mesothelin concentrations were greater than the threshold value of 2.5 nmol/L in the penultimate serum sample before the diagnosis of mesothelioma in 17 of 106 people. Using an increase above the 95% confidence interval of the mean of a given individual's longitudinal mesothelin results, 33 of 82 individuals had increasing mesothelin levels before diagnosis.
In a population with a high pretest probability of developing mesothelioma, the serum biomarker mesothelin is elevated in absolute terms in 15% and in relative terms in 40% of the group.
Future studies examining a combination of biomarkers could improve sensitivity of screening.
恶性间皮瘤是一种侵袭性的、几乎普遍致命的肿瘤，主要由暴露于石棉引起。由于最近发现血清间皮素是间皮瘤的一种敏感且高度特异的生物标志物，因此提出的一个关键问题是间皮素水平是否代表了暴露于石棉的高危个体的有用筛查试验。在这项研究中，在间皮瘤发生之前，测定了暴露于石棉的个体的连续血清样本中的可溶性间皮素。
确定了来自发展为间皮瘤的 106 名个体、来自威滕姆癌症监测计划的 99 名暴露于石棉的个体和来自巴斯顿健康调查的 109 名非暴露于石棉的个体的存档血清样本。使用 MESOMARK 测定法测定血清间皮素浓度。
在 4 年的时间内，对健康的暴露于石棉的个体进行的纵向间皮素水平测定是稳定的（Pearson's r = 0.96；P < 0.0001）。间皮素浓度与累积石棉暴露量之间没有相关性。在 106 人中，有 17 人在诊断为间皮瘤前的倒数第二个血清样本中，间皮素浓度大于 2.5 nmol/L 的阈值。使用给定个体的纵向间皮素结果的 95%置信区间的平均值的增加，在诊断前有 33 名个体的间皮素水平升高。
在具有较高间皮瘤发生前测试概率的人群中，血清生物标志物间皮素在绝对值上有 15%的个体升高，在相对值上有 40%的个体升高。
未来研究检查生物标志物的组合可能会提高筛查的敏感性。
Zotero 插件