Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma.
Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma.
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DOI：
10.1056/nejmoa1115050
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发表时间：
2012-10-11
期刊：
影响因子：
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通讯作者：
Goparaju C
中科院分区：
文献类型：
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作者：
Pass HI;Levin SM;Harbut MR;Melamed J;Chiriboga L;Donington J;Huflejt M;Carbone M;Chia D;Goodglick L;Goodman GE;Thornquist MD;Liu G;de Perrot M;Tsao MS;Goparaju C
新的生物标志物需要在早期阶段检测胸膜间皮瘤和个性化的治疗策略。我们研究了血浆和胸腔积液中的纤维蛋白-3是否能满足一种强有力的生物标志物的敏感性和特异性标准。我们测量了血浆（来自92名间皮瘤患者、136名无癌症石棉暴露者、93名非间皮瘤所致积液患者和43名健康对照者）、积液（来自74名间皮瘤患者、39名良性积液患者和54名非间皮瘤所致恶性积液患者）或两者中的纤维蛋白-3水平。随后进行盲法验证。用免疫组化法检测肿瘤组织中纤维蛋白-3的含量，用酶联免疫吸附法检测血浆和积液中纤维蛋白-3的含量。血浆纤维蛋白-3水平没有因年龄、性别、石棉暴露时间或x线改变程度而变化，胸膜间皮瘤患者（底特律队列为105±7 ng / ml，纽约队列为113±8 ng / ml）比无间皮瘤石棉暴露者（分别为14±1 ng / ml和24±1 ng / ml， P<0.001）明显更高。胸膜间皮瘤患者的积液纤维蛋白-3水平（底特律队列为694±37 ng / ml，纽约队列为636±92 ng / ml）显著高于非间皮瘤患者（分别为212±25和151±23 ng / ml， P<0.001）。在26个样本中，26个样本中纤维蛋白-3优先染色肿瘤细胞。在间皮瘤患者和非间皮瘤患者的总体比较中，血浆纤维蛋白-3水平的受体工作特征曲线在纤维蛋白-3每毫升52.8 ng的临界值下灵敏度为96.7%，特异性为95.5%。在早期间皮瘤患者与石棉暴露者的比较中，灵敏度为100%，特异性为94.1%，临界值为46.0 ng / ml纤维蛋白-3。盲法验证显示，与48例间皮瘤患者相比，96例石棉暴露者血浆标本的曲线下面积为0.87。血浆纤维蛋白-3水平可区分接触石棉的健康人与间皮瘤患者。结合积液纤维蛋白-3水平，血浆纤维蛋白-3水平可以进一步区分间皮瘤积液与其他恶性和良性积液。（由早期检测研究网络、美国国立卫生研究院和其他机构资助。）
New biomarkers are needed to detect pleural mesothelioma at an earlier stage and to individualize treatment strategies. We investigated whether fibulin-3 in plasma and pleural effusions could meet sensitivity and specificity criteria for a robust biomarker. We measured fibulin-3 levels in plasma (from 92 patients with mesothelioma, 136 asbestos-exposed persons without cancer, 93 patients with effusions not due to mesothelioma, and 43 healthy controls), effusions (from 74 patients with mesothelioma, 39 with benign effusions, and 54 with malignant effusions not due to mesothelioma), or both. A blinded validation was subsequently performed. Tumor tissue was examined for fibulin-3 by immunohistochemical analysis, and levels of fibulin-3 in plasma and effusions were measured with an enzyme-linked immunosorbent assay. Plasma fibulin-3 levels did not vary according to age, sex, duration of asbestos exposure, or degree of radiographic changes and were significantly higher in patients with pleural mesothelioma (105±7 ng per milliliter in the Detroit cohort and 113±8 ng per milliliter in the New York cohort) than in asbestos-exposed persons without mesothelioma (14±1 ng per milliliter and 24±1 ng per milliliter, respectively; P<0.001). Effusion fibulin-3 levels were significantly higher in patients with pleural mesothelioma (694±37 ng per milliliter in the Detroit cohort and 636±92 ng per milliliter in the New York cohort) than in patients with effusions not due to mesothelioma (212±25 and 151±23 ng per milliliter, respectively; P<0.001). Fibulin-3 preferentially stained tumor cells in 26 of 26 samples. In an overall comparison of patients with and those without mesothelioma, the receiver-operating-characteristic curve for plasma fibulin-3 levels had a sensitivity of 96.7% and a specificity of 95.5% at a cutoff value of 52.8 ng of fibulin-3 per milliliter. In a comparison of patients with early-stage mesothelioma with asbestos-exposed persons, the sensitivity was 100% and the specificity was 94.1% at a cutoff value of 46.0 ng of fibulin-3 per milliliter. Blinded validation revealed an area under the curve of 0.87 for plasma specimens from 96 asbestos-exposed persons as compared with 48 patients with mesothelioma. Plasma fibulin-3 levels can distinguish healthy persons with exposure to asbestos from patients with mesothelioma. In conjunction with effusion fibulin-3 levels, plasma fibulin-3 levels can further differentiate mesothelioma effusions from other malignant and benign effusions. (Funded by the Early Detection Research Network, National Institutes of Health, and others.)