Serum CA19-9 is significantly upregulated up to 2 years before diagnosis with pancreatic cancer: implications for early disease detection.
Serum CA19-9 is significantly upregulated up to 2 years before diagnosis with pancreatic cancer: implications for early disease detection.
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DOI：
10.1158/1078-0432.ccr-14-0365
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发表时间：
2015-02-01
期刊：
影响因子：
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通讯作者：
Timms JF
中科院分区：
文献类型：
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作者：
O'Brien DP;Sandanayake NS;Jenkinson C;Gentry-Maharaj A;Apostolidou S;Fourkala EO;Camuzeaux S;Blyuss O;Gunu R;Dawnay A;Zaikin A;Smith RC;Jacobs IJ;Menon U;Costello E;Pereira SP;Timms JF
胰腺癌的早期检测迫切需要生物标志物。本研究的主要目的是评估在胰腺癌临床表现之前是否存在血清CA 19 -9、CA 125、CEACAM 1和REG 3A水平升高，并评估联合标志物用于早期检测和预后的性能。这项在UKCTOCS中进行的巢式病例对照研究包括来自154名绝经后妇女的118份单次和143份连续血清样本，这些妇女随后被诊断为胰腺癌，304名匹配的非癌症对照。样本被随机分成独立的训练集和测试集。使用ELISA和/或CLIA测量CA 19 -9、CA 125、CEACAM 1和REG 3A。评估了在诊断前不同时间检测癌症和预后的标志物的性能。在95%的特异性下，CA 19 -9（>37 U/mL）在诊断前1年的灵敏度为68%，在诊断前2年的灵敏度为53%。联合CA 19 -9和CA 125提高了灵敏度，因为在约20%的CA 19 -9阴性病例中CA 125升高（>30 U/mL）。CEACAM 1和REG 3A是晚期标记物，在联合模型中添加很少。估计检测阳性病例的平均准备时间为20-23个月。CA 19 -9和CA 125的诊断前水平与总生存率低相关（HR分别为2.69和3.15）。CA 19 -9和CA 125对于检测临床前胰腺癌具有令人鼓舞的灵敏度，并且这两种标记物可以用作预后工具。这项工作挑战了CA 19 -9在胰腺癌发展过程后期上调的流行观点。
Biomarkers for the early detection of pancreatic cancer are urgently needed. The primary objective of this study was to evaluate whether increased levels of serum CA19-9, CA125, CEACAM1 and REG3A are present prior to clinical presentation of pancreatic cancer and to assess the performance of combined markers for early detection and prognosis. This nested case control study within UKCTOCS included 118 single- and 143 serial-serum samples from 154 post-menopausal women who were subsequently diagnosed with pancreatic cancer and 304 matched non-cancer controls. Samples were split randomly into independent training and test sets. CA19-9, CA125, CEACAM1 and REG3A were measured using ELISA and/or CLIA. Performance of markers to detect cancers at different times prior to diagnosis and for prognosis was evaluated. At 95% specificity, CA19-9 (>37 U/mL) had a sensitivity of 68% up to 1 year, and 53% up to 2 yrs before diagnosis. Combining CA19-9 and CA125 improved sensitivity as CA125 was elevated (>30 U/mL) in ~20% of CA19-9-negative cases. CEACAM1 and REG3A were late markers adding little in combined models. Average lead times of 20-23 months were estimated for test-positive cases. Pre-diagnostic levels of CA19-9 and CA125 were associated with poor overall survival (HR 2.69 and 3.15, respectively). CA19-9 and CA125 have encouraging sensitivity for detecting pre-clinical pancreatic cancer and both markers can be used as prognostic tools. This work challenges the prevailing view that CA19-9 is up-regulated late in the course of pancreatic cancer development.