Creaney Jenette, van Bruggen Ivonne, Hof Michelle, Segal Amanda, Musk Arthur W, de Klerk Nick, Horick Nora, Skates Steven J, Robinson Bruce W S
National Research Centre for Asbestos Related Diseases, 4th Floor, G Block, Sir Charles Gairdner Hospital, Verdun St, Nedlands, WA 6009, Australia.
Chest. 2007 Oct;132(4):1239-46. doi: 10.1378/chest.07-0013. Epub 2007 Jul 23.
Malignant mesothelioma is an aggressive, uniformly fatal tumor. Serum markers would be useful for the diagnosis of this disease. One potential marker is mesothelin. The purpose of this study was to study the mesothelin biomarker in a large patient cohort and to determine if another biomarker, CA125, improves on the sensitivity of mesothelin in the diagnosis of mesothelioma.
Serum levels of mesothelin and CA125 were determined by commercially available assays in 117 samples obtained at diagnosis from patients with pleural malignant mesothelioma, 33 healthy, asbestos-exposed individuals, 53 patients with asbestos-related lung or pleural disease, and 30 patients presenting with benign pleural effusions. Cross-validated sensitivities were determined, and receiver operator characteristic curves were generated to compare the diagnostic accuracy of the biomarkers.
CA125 had a cross-validated sensitivity of 27% for mesothelioma patients at a specificity of 95% relative to asbestos-exposed individuals, or 50% relative to individuals with benign pleural effusions. Mesothelin had a cross-validated sensitivity of 52% for mesothelioma patients, at a sensitivity of 95% relative to individuals with benign lung or pleural disease. CA125 and mesothelin levels were discordant in > 50% of mesothelioma patients. Combining the data from the two biomarkers using a logistic regression model did not improve sensitivity for detecting mesothelioma above that of the mesothelin marker alone.
Combining mesothelin and CA125 data does not improve the sensitivity of mesothelioma diagnosis over mesothelin alone. The use of both markers potentially increases the number of patients who can be monitored.
恶性间皮瘤是一种侵袭性强、无一例外会导致死亡的肿瘤。血清标志物对该疾病的诊断会有帮助。一种潜在的标志物是间皮素。本研究的目的是在一个大型患者队列中研究间皮素生物标志物，并确定另一种生物标志物CA125是否能提高间皮素在间皮瘤诊断中的敏感性。
采用市售检测方法测定了117份诊断时采集的样本中的间皮素和CA125血清水平，这些样本来自胸膜恶性间皮瘤患者、33名健康的石棉接触者、53名患有石棉相关肺部或胸膜疾病的患者以及30名出现良性胸腔积液的患者。确定交叉验证的敏感性，并生成受试者工作特征曲线以比较生物标志物的诊断准确性。
相对于石棉接触者，CA125对间皮瘤患者的交叉验证敏感性为27%，特异性为95%；相对于良性胸腔积液患者，敏感性为50%。间皮素对间皮瘤患者的交叉验证敏感性为52%，相对于患有良性肺部或胸膜疾病的个体，敏感性为95%。在超过50%的间皮瘤患者中，CA125和间皮素水平不一致。使用逻辑回归模型合并两种生物标志物的数据并没有提高检测间皮瘤的敏感性，高于单独使用间皮素标志物时的敏感性。
合并间皮素和CA125的数据并不能比单独使用间皮素提高间皮瘤诊断的敏感性。同时使用这两种标志物可能会增加可监测患者的数量。
