Simon Iris, Liu Yan, Krall Kirstin L, Urban Nicole, Wolfert Robert L, Kim Nam W, McIntosh Martin W
diaDexus, Inc., 343 Oyster Point Blvd., South San Francisco, CA 94080, USA.
Gynecol Oncol. 2007 Jul;106(1):112-8. doi: 10.1016/j.ygyno.2007.03.007. Epub 2007 May 8.
Early detection through regular screening could significantly reduce mortality from ovarian cancer. Advances in biomarkers and imaging continue to improve the sensitivity and specificity of cancer detection, but further improvements are still needed. In this study, we identified and evaluated three new serum biomarkers that may be used to improve detection of ovarian cancer.
Through genomic analysis, we identified B7-H4, Spondin 2, and DcR3 as over-expressed genes in ovarian cancer tissues. Sensitive sandwich ELISAs were developed to analyze the level of these novel markers in 68 serum samples from patients with ovarian cancer (16 early stage, 52 late stage) and 108 control samples, and 20 healthy women from which two serum samples were collected 1 year apart. CA125 levels were measured in all samples.
Markers were evaluated for their ability to identify clinical disease. The three novel markers and CA125 were elevated in serum of ovarian cancer patients as compared to normal controls. B7-H4 showed the highest specificity, with the lowest frequency of elevation in all control groups. When all cases were compared against all controls, CA125, Spondin 2, B7-H4, and DcR3 showed areas under the ROC curve of 0.87, 0.78, 0.74, and 0.71, respectively. CA125 and B7-H4 showed the best diagnostic performance for early-stage, with AUCs of 0.90 and 0.80, respectively.
This study demonstrates that B7-H4, Spondin 2, and DcR3 are promising new ovarian cancer markers that may improve early detection of cancer when used in combination with traditional diagnostic tests.
通过定期筛查进行早期检测可显著降低卵巢癌死亡率。生物标志物和成像技术的进步不断提高癌症检测的敏感性和特异性，但仍需进一步改进。在本研究中，我们鉴定并评估了三种可能用于改善卵巢癌检测的新型血清生物标志物。
通过基因组分析，我们确定B7-H4、Spondin 2和DcR3为卵巢癌组织中过表达的基因。开发了灵敏的夹心酶联免疫吸附测定法（ELISA），以分析来自卵巢癌患者（16例早期、52例晚期）的68份血清样本、108份对照样本以及20名健康女性（相隔1年采集两份血清样本）中这些新型标志物的水平。对所有样本测量CA125水平。
评估了这些标志物识别临床疾病的能力。与正常对照相比，卵巢癌患者血清中的三种新型标志物和CA125均升高。B7-H4显示出最高的特异性，在所有对照组中升高频率最低。当将所有病例与所有对照进行比较时，CA125、Spondin 2、B7-H4和DcR3的ROC曲线下面积分别为0.87、0.78、0.74和0.71。CA125和B7-H4对早期阶段显示出最佳诊断性能，AUC分别为0.90和0.80。
本研究表明，B7-H4、Spondin 2和DcR3是有前景的新型卵巢癌标志物，与传统诊断测试联合使用时可能改善癌症的早期检测。
