Validation of biomarkers that complement CA19.9 in detecting early pancreatic cancer.
Validation of biomarkers that complement CA19.9 in detecting early pancreatic cancer.
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DOI：
10.1158/1078-0432.ccr-14-0289
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发表时间：
2014-11-15
期刊：
影响因子：
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通讯作者：
Blasutig IM
中科院分区：
文献类型：
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作者：
Chan A;Prassas I;Dimitromanolakis A;Brand RE;Serra S;Diamandis EP;Blasutig IM
胰腺导管腺癌（PDAC）是癌症死亡的重要原因。CA19.9是唯一可用于检测和监测PDAC的肿瘤标志物，但其敏感性和特异性不足以持续区分早期癌症和良性疾病。在本研究中，我们旨在验证最近发现的用于PDAC早期检测的血清蛋白生物标志物，并最终开发一种生物标志物面板，可以比现有标志物CA19.9更好地区分PDAC与其他良性疾病。我们对从连续招募的个体中收集的400份血清样本进行了回顾性盲法评估。样本群体包括250名不同阶段的PDAC个体，130名良性个体和20名健康个体。采用elisa或自动免疫分析法测定血清中各生物标志物的水平。通过将匹配样本随机分成训练组（n=186）和验证组（n=214），我们能够开发并验证由CA19.9、CA125和LAMC2组成的生物标志物面板，该面板显著提高了单独CA19.9的性能。在验证集中，所有PDAC与良性疾病（AUCCA19.9=0.80, AUCCA19.9+CA125+LAMC2= 0.87, p<0.005）、早期PDAC与良性疾病（AUCCA19.9= 0.69, AUCCA19.9+CA125+LAMC2= 0.76, p<0.05）、早期PDAC与慢性胰腺炎（AUCCA19.9= 0.59, AUCCA19.9+CA125+LAMC2= 0.74, p<0.05）之间的区别有所改善。这些数据表明，由CA125、CA19.9和LAMC2组成的血清蛋白生物标志物组在检测PDAC时能够显著提高单独使用CA19.9的性能。
Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer mortality. CA19.9, the only tumor marker available to detect and monitor PDAC, is not sufficiently sensitive and specific to consistently differentiate early cancer from benign disease. In this study we aimed to validate recently discovered serum protein biomarkers for the early detection of PDAC and ultimately develop a biomarker panel that could discriminate PDAC from other benign disease better than the existing marker CA19.9. We performed a retrospective blinded evaluation of 400 serum samples collected from individuals recruited on a consecutive basis. The sample population consisted of 250 individuals with PDAC at various stages, 130 individuals with benign conditions and 20 healthy individuals. The serum levels of each biomarker were determined by ELISAs or automated immunoassay. By randomly splitting matched samples into a training (n=186) and validation (n=214) set we were able to develop and validate a biomarker panel consisting of CA19.9, CA125 and LAMC2 that significantly improved the performance of CA19.9 alone. Improved discrimination was observed in the validation set between all PDAC and benign conditions (AUCCA19.9=0.80 versus AUCCA19.9+CA125+LAMC2= 0.87; p<0.005) as well as between early-stage PDAC and benign conditions (AUCCA19.9 = 0.69 versus AUCCA19.9+CA125+LAMC2 = 0.76; p<0.05) and between early-stage PDAC and chronic pancreatitis (AUCCA19.9 = 0.59 versus AUCCA19.9+CA125+LAMC2 = 0.74; p<0.05). The data demonstrate that a serum protein biomarker panel consisting of CA125, CA19.9 and LAMC2 is able to significantly improve upon the performance of CA19.9 alone in detecting PDAC.