鈣結合蛋白可作為間皮瘤的血液生物標誌物

論文題目：Calretinin as a blood-based biomarker for mesothelioma

作者：Georg Johnen et al.

數字識別碼：10.1186/s12885-017-3375-5

惡性間皮瘤（MM）是一種主要由接觸石棉引起的致命癌症，潛伏期長達50年。即使在禁用石棉的國家，惡性間皮瘤的發病率仍在上升。目前已經建立了為高風險人群提供定期健康檢查的二級預防體系。應用腫瘤標誌物進行更早期檢測可能有助於改善治療方式。之前我們開發了一種新的檢測血液中特定蛋白標誌物—鈣結合蛋白的方法。這項研究旨在在一組獨立的研究人群中驗證該檢測方法，並與已建立的標誌物間皮素進行比較。

近期在BMC Cancer發表了題目為Calretinin as a blood-based biomarker for mesothelioma的研究。本研究為一項針對男性的病例對照研究，共納入來自澳大利亞的163例胸膜惡性間皮瘤患者和163例對照者，以及來自德國的36例惡性間皮瘤患者和72例對照者。所有對照者均有石棉肺和/或斑塊。在治療前收集受試者的血清或血漿，並通過ELISA（酶聯免疫吸附測定）法測定鈣結合蛋白和間皮素水平。我們評估了兩種標誌物的表現，以及可能影響標誌物濃度的因素，如年齡、樣本儲存時間和惡性間皮瘤亞型。

鈣結合蛋白能夠檢測除肉瘤樣惡性間皮瘤以外的其他所有主要亞型。在澳大利亞和德國男性中，鈣結合蛋白有類似的表現。在預設的特異性為95%時，除肉瘤樣惡性間皮瘤外，鈣結合蛋白的敏感性達到71%，間皮素的敏感性達到69%。在特異性為97%時，與鈣結合蛋白結合可使間皮素的敏感性從66%提高至75%。樣品儲存時間不影響結果。在對照組中，年齡每增加10歲，鈣結合蛋白的濃度增加1.87倍（95%可信區間：1.10-3.20），間皮素的增加程度略高（為2.28倍，95%可信區間：1.30-4.00）。

經驗證，鈣結合蛋白可作為惡性間皮瘤的血液生物標誌物。該檢測方法的靈敏性較高，並且與間皮素的表現相當。回顧性分析不會受到儲存時間的限制。高特異性使得鈣結合蛋白能夠與其他標誌物聯合使用。鈣結合蛋白對上皮樣和雙相型間皮瘤具有特異性，但對罕見的肉瘤樣亞型無特異性。諸如鈣結合蛋白和間皮素等分子標誌物是有望改善和補充間皮瘤診斷的工具，未來還需要在前瞻性研究中進一步驗證。

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.

期刊介紹：BMC Canceris an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.

2016 Journal Metrics

Citation Impact

3.288 - 2-year Impact Factor

3.645 - 5-year Impact Factor

1.078 - Source Normalized Impact per Paper (SNIP)

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