论文题目：Calretinin as a blood-based biomarker for mesothelioma

期刊：

作者：Georg Johnen et al.

发表时间：2017/5/30

数字识别码：10.1186/s12885-017-3375-5

原文链接：

恶性间皮瘤（MM）是一种主要由接触石棉引起的致命癌症，潜伏期长达50年。即使在禁用石棉的国家，恶性间皮瘤的发病率仍在上升。目前已经建立了为高风险人群提供定期健康检查的二级预防体系。应用肿瘤标志物进行更早期检测可能有助于改善治疗方式。之前我们开发了一种新的检测血液中特定蛋白标志物—钙结合蛋白的方法。这项研究旨在在一组独立的研究人群中验证该检测方法，并与已建立的标志物间皮素进行比较。

近期在BMC Cancer发表了题目为Calretinin as a blood-based biomarker for mesothelioma的研究。本研究为一项针对男性的病例对照研究，共纳入来自澳大利亚的163例胸膜恶性间皮瘤患者和163例对照者，以及来自德国的36例恶性间皮瘤患者和72例对照者。所有对照者均有石棉肺和/或斑块。在治疗前收集受试者的血清或血浆，并通过ELISA（酶联免疫吸附测定）法测定钙结合蛋白和间皮素水平。我们评估了两种标志物的表现，以及可能影响标志物浓度的因素，如年龄、样本储存时间和恶性间皮瘤亚型。

钙结合蛋白能够检测除肉瘤样恶性间皮瘤以外的其他所有主要亚型。在澳大利亚和德国男性中，钙结合蛋白有类似的表现。在预设的特异性为95%时，除肉瘤样恶性间皮瘤外，钙结合蛋白的敏感性达到71%，间皮素的敏感性达到69%。在特异性为97%时，与钙结合蛋白结合可使间皮素的敏感性从66%提高至75%。样品储存时间不影响结果。在对照组中，年龄每增加10岁，钙结合蛋白的浓度增加1.87倍（95%可信区间：1.10-3.20），间皮素的增加程度略高（为2.28倍，95%可信区间：1.30-4.00）。

经验证，钙结合蛋白可作为恶性间皮瘤的血液生物标志物。该检测方法的灵敏性较高，并且与间皮素的表现相当。回顾性分析不会受到储存时间的限制。高特异性使得钙结合蛋白能够与其他标志物联合使用。钙结合蛋白对上皮样和双相型间皮瘤具有特异性，但对罕见的肉瘤样亚型无特异性。诸如钙结合蛋白和间皮素等分子标志物是有望改善和补充间皮瘤诊断的工具，未来还需要在前瞻性研究中进一步验证。

摘要：

Background

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.

Methods

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.

Results

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).

Conclusions

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.

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