Serum protein markers for early detection of ovarian cancer
Serum protein markers for early detection of ovarian cancer
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DOI：
10.1073/pnas.0502178102
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发表时间：
2005-05-24
影响因子：
11.1
通讯作者：
Ward, DC
中科院分区：
文献类型：
--
作者：
Mor, G;Visintin, I;Ward, DC
上皮性卵巢癌（EOC）的早期诊断将显著降低该病的发病率和死亡率，但在没有身体症状的情况下很难诊断。在这里，我们报告了一种血液测试，基于同时定量的四种分析物（瘦素、催乳素、骨桥蛋白和胰岛素样生长因子II），可以区分无病和EOC患者，包括诊断为I期和II期疾病的患者，效率很高（95%）。微阵列分析最初用于测定28名健康妇女、18名新诊断为EOC的妇女和40名复发性疾病妇女的血清中169种蛋白质的水平。通过酶联免疫吸附试验对对照组和癌症患者之间表达有显著差异的蛋白质进行评估，得出了这四种分析物。然后在一项盲交叉验证研究中对这四种蛋白进行了评估，该研究使用了另外106名健康女性和100名EOC患者（24名I/II期患者和76名III/IV期患者）。在样本解码后，使用三种不同的分类算法和二进制编码方法分析结果。通过使用另外40例正常和EOC癌症患者的血清样本，四分析物测试在盲二进制代码研究中得到进一步验证。没有一种蛋白质可以完全区分癌症组和健康对照组。然而，四种分析物的组合表现出以下特征：敏感性95%，阳性预测值（PPV） 95%，特异性95%，阴性预测值（NPV） 94%，这是对当前方法的重大改进。
Early diagnosis of epithelial ovarian cancer (EOC) would significantly decrease the morbidity and mortality from this disease but is difficult in the absence of physical symptoms. Here, we report a blood test, based on the simultaneous quantization of four analytes (leptin, prolactin, osteopontin, and insulin-like growth factor-II), that can discriminate between disease-free and EOC patients, including patients diagnosed with stage I and II disease, with high efficiency (95%). Microarray analysis was used initially to determine the levels of 169 proteins in serum from 28 healthy women, 18 women newly diagnosed with EOC, and 40 women with recurrent disease. Evaluation of proteins that showed significant differences in expression between controls and cancer patients by ELISA assays yielded the four analytes. These four proteins then were evaluated in a blind cross-validation study by using an additional 106 healthy females and 100 patients with EOC(24 stage I/II and 76 stage III/IV). Upon sample decoding, the results were analyzed by using three different classification algorithms and a binary code methodology. The four-analyte test was further validated in a blind binary code study by using 40 additional serum samples from normal and EOC cancer patients. No single protein could completely distinguish the cancer group from the healthy controls. However, the combination of the four analytes exhibited the following: sensitivity 95%, positive predictive value (PPV) 95%, specificity 95%, and negative predictive value (NPV) 94%, a considerable improvement on current methodology.