Fedarko N S, Jain A, Karadag A, Van Eman M R, Fisher L W
Division of Geriatrics, Department of Medicine, The Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
Clin Cancer Res. 2001 Dec;7(12):4060-6.
Histological studies have shown that the two sialoproteins, bone sialoprotein (BSP) and osteopontin (OPN), are induced in multiple types of cancer. We have recently found that these proteins are bound in serum to complement factor H and that the complex must be disrupted to generate free protein to measure their total levels. We hypothesized that measuring total BSP and OPN levels would provide informative markers for the detection of cancer.
As a proof of concept study, serum from patients with diagnosed breast, colon, lung, or prostate cancer (n = 20 for each type) as well as normal serum (n = 77) were analyzed using competitive ELISAs developed for BSP and OPN. Sensitivity, specificity, as well as positive and negative predictive values were determined for each sialoprotein and cancer type. The relationship between sensitivity and specificity was profiled by receiver operating characteristic curves.
Determined values for serum BSP in ng/ml were 285 +/- 19 for prostate, 373 +/- 19 for colon, 318 +/- 18 for breast, 155 +/- 11 for lung cancer sera, and 154 +/- 13 for normal sera. Values of OPN in ng/ml were 653 +/- 39 for prostate, 449 +/- 22 for colon, 814 +/- 53 for breast, 724 +/- 33 for lung, and 439 +/- 30 for normal sera. The assays provide a high degree of sensitivity and specificity that enables the detection of colon, breast, prostate, and lung cancer.
组织学研究表明，两种唾液酸蛋白，即骨唾液酸蛋白（BSP）和骨桥蛋白（OPN），在多种类型的癌症中被诱导产生。我们最近发现，这些蛋白在血清中与补体因子H结合，并且必须破坏该复合物才能产生游离蛋白以测量其总水平。我们假设测量总BSP和OPN水平将为癌症检测提供有用的标志物。
作为概念验证研究，使用针对BSP和OPN开发的竞争性酶联免疫吸附测定（ELISA）分析了已确诊的乳腺癌、结肠癌、肺癌或前列腺癌患者的血清（每种类型n = 20）以及正常血清（n = 77）。确定了每种唾液酸蛋白和癌症类型的敏感性、特异性以及阳性和阴性预测值。通过受试者工作特征曲线描绘了敏感性和特异性之间的关系。
前列腺癌血清中BSP的测定值为285±19 ng/ml，结肠癌为373±19 ng/ml，乳腺癌为318±18 ng/ml，肺癌血清为155±11 ng/ml，正常血清为154±13 ng/ml。OPN的测定值在前列腺癌血清中为653±39 ng/ml，结肠癌为449±22 ng/ml，乳腺癌为814±53 ng/ml，肺癌为724±33 ng/ml，正常血清为439±30 ng/ml。这些检测方法具有高度的敏感性和特异性，能够检测出结肠癌、乳腺癌、前列腺癌和肺癌。
