Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany.
Sci Rep. 2018 Sep 25;8(1):14321. doi: 10.1038/s41598-018-32315-3.
Malignant mesothelioma (MM) is strongly associated with a previous asbestos exposure. To improve timely detection of MM in asbestos workers, better screening tools - like minimally-invasive biomarkers - are desirable. Between 2008 and 2018 2,769 patients with benign asbestos-related diseases were recruited to participate in annual screens. Using a nested case-control design the protein markers calretinin and mesothelin were determined by enzyme-linked immunosorbent assays in prediagnostic plasma samples of 34 MM cases as well as 136 matched controls from the cohort. Conditional on a pre-defined specificity of 98% for calretinin and 99% for mesothelin the markers reached individual sensitivities of 31% and 23%, respectively, when including the incident cases with samples taken between one and 15 months before diagnosis. The combination of both markers increased the sensitivity to 46% at 98% specificity. Marker complementation increased with earlier sampling. The marker combination improves the sensitivity of the individual markers, indicating a useful complementation and suggesting that additional markers may further improve the performance. This is the first prospective cohort study to evaluate a detection of MM by calretinin and its combination with mesothelin up to about a year before clinical diagnosis. Whether an earlier diagnosis will result in reduced mortality has yet to be demonstrated.
恶性间皮瘤（MM）与既往石棉暴露密切相关。为了提高石棉作业工人中 MM 的及时检出率，人们希望使用微创生物标志物等更好的筛查工具。2008 年至 2018 年，招募了 2769 名良性石棉相关疾病患者参加年度筛查。采用巢式病例对照设计，在 34 例 MM 病例和队列中的 136 例匹配对照的预测前血浆样本中，通过酶联免疫吸附试验测定钙结合蛋白和间皮素这两种蛋白标志物。在预先设定的钙结合蛋白特异性为 98%和间皮素特异性为 99%的条件下，当包括在诊断前 1 至 15 个月采集样本的新发病例时，这两种标志物的个体敏感性分别为 31%和 23%。两种标志物联合使用时，特异性为 98%时的敏感性提高到 46%。随着采样时间更早，标志物互补性增加。标志物组合提高了个体标志物的敏感性，表明其具有有用的互补性，并提示可能有其他标志物进一步提高其性能。这是第一项前瞻性队列研究，评估了在临床诊断前约一年通过钙结合蛋白及其与间皮素的组合检测 MM 的情况。早期诊断是否会降低死亡率，还有待证实。
