Systematic evaluation of candidate blood markers for detecting ovarian cancer.
Systematic evaluation of candidate blood markers for detecting ovarian cancer.
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DOI：
10.1371/journal.pone.0002633
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发表时间：
2008-07-09
期刊：
影响因子：
3.7
通讯作者：
Urban N
中科院分区：
文献类型：
--
作者：
Palmer C;Duan X;Hawley S;Scholler N;Thorpe JD;Sahota RA;Wong MQ;Wray A;Bergan LA;Drescher CW;McIntosh MW;Brown PO;Nelson BH;Urban N
上皮性卵巢癌是美国和世界范围内死亡率的重要原因，主要是由于晚期病例的比例很高，此时生存率极低。早期发现上皮性卵巢癌，特别是浆液性卵巢癌，是挽救生命的一个有希望的策略。卵巢癌的低患病率使得基于血液标志物的足够敏感和特异性测试的开发非常具有挑战性。我们评估了一组候选血液标志物和这些标志物的组合在检测浆液性卵巢癌中的性能。基于我们对全球基因表达数据的分析和文献检索，我们选择了14种浆液性卵巢癌的候选血液标志物，这些标志物的检测方法可用于测量其在血清或血浆中的水平。我们评估了这些候选标志物的性能，单独和组合，通过测量它们在重叠的血清（或血浆）样本集，从妇女临床可检测卵巢癌和妇女卵巢癌。基于高特异性的灵敏度，我们确定了14个候选标记物中的4个-MUC 16、WFDC 2、MSLN和MMP 7--需要在临床诊断前数月至数年收集的珍贵血清标本中进行进一步评估，以评估其在早期检测中的效用。我们还报道了这些候选血液标志物在上皮性卵巢癌组织学类型中的表现差异。通过系统分析卵巢癌候选血液标志物在区分临床上明显的卵巢癌妇女与非卵巢癌妇女方面的性能，我们确定了一组具有足够性能的血清标志物，以保证在临床诊断前数月至数年检测其识别卵巢癌的能力。我们认为，敏感性在高特异性的重要性，并在病例和对照组之间的标记物水平的差异幅度作为性能指标，并证明了分层分析的重要性，卵巢癌的组织学类型。此外，我们讨论了研究的局限性（如本研究），使用从有症状的妇女获得的样本，以评估在临床检测前数月至数年检测疾病的潜在效用。
Epithelial ovarian cancer is a significant cause of mortality both in the United States and worldwide, due largely to the high proportion of cases that present at a late stage, when survival is extremely poor. Early detection of epithelial ovarian cancer, and of the serous subtype in particular, is a promising strategy for saving lives. The low prevalence of ovarian cancer makes the development of an adequately sensitive and specific test based on blood markers very challenging. We evaluated the performance of a set of candidate blood markers and combinations of these markers in detecting serous ovarian cancer. We selected 14 candidate blood markers of serous ovarian cancer for which assays were available to measure their levels in serum or plasma, based on our analysis of global gene expression data and on literature searches. We evaluated the performance of these candidate markers individually and in combination by measuring them in overlapping sets of serum (or plasma) samples from women with clinically detectable ovarian cancer and women without ovarian cancer. Based on sensitivity at high specificity, we determined that 4 of the 14 candidate markers-MUC16, WFDC2, MSLN and MMP7-warrant further evaluation in precious serum specimens collected months to years prior to clinical diagnosis to assess their utility in early detection. We also reported differences in the performance of these candidate blood markers across histological types of epithelial ovarian cancer. By systematically analyzing the performance of candidate blood markers of ovarian cancer in distinguishing women with clinically apparent ovarian cancer from women without ovarian cancer, we identified a set of serum markers with adequate performance to warrant testing for their ability to identify ovarian cancer months to years prior to clinical diagnosis. We argued for the importance of sensitivity at high specificity and of magnitude of difference in marker levels between cases and controls as performance metrics and demonstrated the importance of stratifying analyses by histological type of ovarian cancer. Also, we discussed the limitations of studies (like this one) that use samples obtained from symptomatic women to assess potential utility in detection of disease months to years prior to clinical detection.
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影响因子：
11.2
作者：
Sunde, Jan S.;Donninger, Howard;Birrer, Michael J.
通讯作者：
Birrer, Michael J.
影响因子：
45.3
作者：
Dupont, J;Tanwar, MK;Spriggs, DR
通讯作者：
Spriggs, DR
影响因子：
12.3
作者：
Shyamsundar R;Kim YH;Higgins JP;Montgomery K;Jorden M;Sethuraman A;van de Rijn M;Botstein D;Brown PO;Pollack JR
通讯作者：
Pollack JR
DOI：
10.1073/pnas.0502178102
发表时间：
2005-05-24
影响因子：
11.1
作者：
Mor, G;Visintin, I;Ward, DC
通讯作者：
Ward, DC
影响因子：
11.5
作者：
Scholler, N;Crawford, M;Urban, N
通讯作者：
Urban, N