来自英国伦敦大学学院(The University College London)和利物浦大学(The University of Liverpool)的研究人员最近发现了两个新的血液肿瘤标志物，可作为早期筛查工具，提前最长2年诊断胰腺癌。这个研究发表在最新的Clinical Cancer Research。

        科研人员进行了大量的病例对照研究。研究收集了154位已经绝经的妇女被诊断为胰腺癌之前的118个单独的和143个系列的血清样品，并使用另外304个匹配但是未患肿瘤的样品作为对照。实验主要使用Elisa或者CLIA测量血清CA19-9，CA125，CEACAM1和REG3A含量，以检测这几个潜在标志物在胰腺癌诊断前不同时间的表达模式，与疾病预后是否相关。

        研究发现CEACAM1和REG3A在早期变化不明显。而CA19-9(> 37 U / mL)在胰腺癌发病前一年，有68%的敏感性，发病前两年，敏感性为53%。结合CA125和CA19-9，可以增高检测灵敏度—CA19-9阴性的病人有20%出现CA125升高(> 30 U / ml)。并且CA19-9与CA123诊断前水平和病发后生存期有一定关系，风险比(Hazard Ratio)分别是2.69 与3.15。

        以上实验证明CA19-9与CA125可结合作为临床胰腺癌早期诊断和预测疾病预后的指标。其实以前已经有研究发现CA19-9的在胰腺癌发展中晚期水平才会上调。这次研究证实疾病早期同样有CA19-9血清含量上升。不过CA19-9水平增加也存在假阳性结果，比如患有胰腺炎和梗阻性黄疸的时候。

        胰腺癌患者>五年的生存率仅仅只有4%。所以这对能帮助早期诊断和预测预后的新组合标志物的发现，绝对是个令人兴奋的消息。

        doi: 10.1158/1078-0432.CCR-14-0365

Serum CA19-9 Is Significantly Upregulated up to 2 Years before Diagnosis with Pancreatic Cancer: Implications for Early Disease Detection

        Darragh P. O'Brien, Neomal S. Sandanayake, Claire Jenkinson, Aleksandra Gentry-Maharaj, Sophia Apostolidou, Evangelia-Ourania Fourkala, Stephane Camuzeaux, Oleg Blyuss, Richard Gunu, Anne Dawnay, Alexey Zaikin, Ross C. Smith, Ian J. Jacobs Usha Menon, Eithne Costello, Stephen P. Pereira and John F. Timms

        Abstract

        Purpose: 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 before clinical presentation of pancreatic cancer and to assess the performance of combined markers for early detection and prognosis.

        Experimental Design: This nested case-control study within the UKCTOCS included 118 single and 143 serial serum samples from 154 postmenopausal women who were subsequently diagnosed with pancreatic cancer and 304 matched noncancer 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 before diagnosis and for prognosis was evaluated.

        Results: At 95% specificity, CA19-9 (>37 U/mL) had a sensitivity of 68% up to 1 year, and 53% up to 2 years before diagnosis. Combining CA19-9 and CA125 improved sensitivity as CA125 was elevated (>30 U/mL) in approximately 20% of CA19-9-negative cases. CEACAM1 and REG3A were late markers adding little in combined models. Average lead times of 20 to 23 months were estimated for test-positive cases. Prediagnostic levels of CA19-9 and CA125 were associated with poor overall survival (HR, 2.69 and 3.15, respectively).