Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women
Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women
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DOI：
10.3390/cancers12071931
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发表时间：
2020-07-01
期刊：
影响因子：
5.2
通讯作者：
Menon, Usha
中科院分区：
文献类型：
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作者：
Gentry-Maharaj, Aleksandra;Blyuss, Oleg;Menon, Usha
纵向CA 125算法是目前卵巢癌筛查的基础。我们报告的纵向算法，将多个标记。在英国卵巢癌筛查合作试验（UKCTOCS）的多模式组中，50，640名绝经后妇女使用血清CA 125纵向算法进行年度筛查。在对诊断前5年内捐献的年度血清样本进行结局审查后，浸润性输卵管卵巢癌（WHO 2014）女性（病例）与对照组（无浸润性输卵管卵巢癌）在年度样本数量和随机化年龄方面1：1匹配。测定设盲样本的血清人附睾蛋白4（HE 4）、CA 72 -4和抗TP 53自身抗体。使用训练集上的试验结果和试验CA 125值开发了多标志物平均趋势法（MMT）纵向算法，并在设盲验证集中进行了评价。研究集包括来自179例病例和181例对照的1363个（每个妇女2-5个）系列样本。在验证集中，纵向CA 125-MMT算法的曲线下面积（AUC）和灵敏度分别为0.911（0.871-0.952）和90.5%（82.5-98.6%）。纵向多标记算法（CA 125-HE 4、CA 125-HE 4-CA 72 -4、CA 125-HE 4-CA 72 -4-anti-TP 53）在前置时间方面均未表现更好或有所改善。我们的人群研究表明，纵向HE 4，CA 72 -4，抗TP 53自身抗体添加纵向血清CA 125作为绝经后妇女卵巢癌筛查的一线测试的价值不大。
Longitudinal CA125 algorithms are the current basis of ovarian cancer screening. We report on longitudinal algorithms incorporating multiple markers. In the multimodal arm of United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 50,640 postmenopausal women underwent annual screening using a serum CA125 longitudinal algorithm. Women (cases) with invasive tubo-ovarian cancer (WHO 2014) following outcome review with stored annual serum samples donated in the 5 years preceding diagnosis were matched 1:1 to controls (no invasive tubo-ovarian cancer) in terms of the number of annual samples and age at randomisation. Blinded samples were assayed for serum human epididymis protein 4 (HE4), CA72-4 and anti-TP53 autoantibodies. Multimarker method of mean trends (MMT) longitudinal algorithms were developed using the assay results and trial CA125 values on the training set and evaluated in the blinded validation set. The study set comprised of 1363 (2-5 per woman) serial samples from 179 cases and 181 controls. In the validation set, area under the curve (AUC) and sensitivity of longitudinal CA125-MMT algorithm were 0.911 (0.871-0.952) and 90.5% (82.5-98.6%). None of the longitudinal multi-marker algorithms (CA125-HE4, CA125-HE4-CA72-4, CA125-HE4-CA72-4-anti-TP53) performed better or improved on lead-time. Our population study suggests that longitudinal HE4, CA72-4, anti-TP53 autoantibodies adds little value to longitudinal serum CA125 as a first-line test in ovarian cancer screening of postmenopausal women.