Johnen Georg, Gawrych Katarzyna, Raiko Irina, Casjens Swaantje, Pesch Beate, Weber Daniel G, Taeger Dirk, Lehnert Martin, Kollmeier Jens, Bauer Torsten, Musk Arthur W, Robinson Bruce W S, Brüning Thomas, Creaney Jenette
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Institute of the Ruhr University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
Lungenklinik Heckeshorn, HELIOS Clinic Emil von Behring, Berlin, Germany.
BMC Cancer. 2017 May 30;17(1):386. doi: 10.1186/s12885-017-3375-5.
Malignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin.
For a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performance of both markers and tested factors potentially influencing marker concentrations like age, sample storage time, and MM subtype.
Calretinin was able to detect all major subtypes except for sarcomatoid MM. Calretinin showed a similar performance in Australian and German men. At a pre-defined specificity of 95% the sensitivity of calretinin reached 71% and that of mesothelin 69%, when excluding sarcomatoid MM. At 97% specificity, the combination with calretinin increased the sensitivity of mesothelin from 66% to 75%. Sample storage time did not influence the results. In controls the concentrations of calretinin increased 1.87-fold (95% CI 1.10-3.20) per 10 years of age and slightly more for mesothelin (2.28, 95% CI 1.30-4.00).
Calretinin could be verified as a blood-based marker for MM. The assay is robust and shows a performance that is comparable to that of mesothelin. Retrospective analyses would not be limited by storage time. The high specificity supports a combination of calretinin with other markers. Calretinin is specific for epithelioid and biphasic MM but not the rarer sarcomatoid form. Molecular markers like calretinin and mesothelin are promising tools to improve and supplement the diagnosis of MM and warrant further validation in a prospective study.
恶性间皮瘤（MM）是一种致命癌症，主要由既往接触石棉所致。由于潜伏期长达50年，即使在已禁止使用石棉的国家，MM的发病率仍在上升。二级预防已确立，为有风险的人群提供定期健康检查。利用肿瘤标志物进行早期检测可能会改善治疗选择。此前，我们已开发出一种针对蛋白质标志物钙视网膜蛋白的新型血液检测方法。本研究的目的是在一个独立的研究人群中验证该检测方法，并与已确立的标志物间皮素进行比较。
在一项针对男性的病例对照研究中，从澳大利亚获得了163例胸膜MM病例和163例对照，在德国又招募了36例病例和72例对照。所有对照均患有石棉肺和/或胸膜斑。在治疗前采集的血清或血浆中，通过酶联免疫吸附测定（ELISA）法测定钙视网膜蛋白和间皮素。我们评估了这两种标志物的性能，并测试了可能影响标志物浓度的因素，如年龄、样本储存时间和MM亚型。
钙视网膜蛋白能够检测除肉瘤样MM之外的所有主要亚型。在澳大利亚和德国男性中，钙视网膜蛋白表现出相似的性能。在排除肉瘤样MM后，当预定义特异性为95%时，钙视网膜蛋白的敏感性达到71%，间皮素的敏感性为69%。在特异性为97%时，钙视网膜蛋白与间皮素联合使用可使间皮素的敏感性从66%提高到75%。样本储存时间不影响结果。在对照中，钙视网膜蛋白的浓度每增加10岁增加1.87倍（95%可信区间1.10 - 3.20），间皮素增加幅度略大（2.28，95%可信区间1.30 - 4.00）。
钙视网膜蛋白可被验证为MM的一种血液标志物。该检测方法可靠，其性能与间皮素相当。回顾性分析不会受到储存时间的限制。高特异性支持钙视网膜蛋白与其他标志物联合使用。钙视网膜蛋白对上皮样和双相性MM具有特异性，但对较罕见的肉瘤样形式不具有特异性。像钙视网膜蛋白和间皮素这样的分子标志物是改善和补充MM诊断的有前景的工具，值得在前瞻性研究中进一步验证。
