The Ludwig Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287.
Howard Hughes Medical Institute, The Johns Hopkins Medical Institutions, Baltimore, MD 21287.
Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10202-10207. doi: 10.1073/pnas.1704961114. Epub 2017 Sep 5.
The earlier diagnosis of cancer is one of the keys to reducing cancer deaths in the future. Here we describe our efforts to develop a noninvasive blood test for the detection of pancreatic ductal adenocarcinoma. We combined blood tests for gene mutations with carefully thresholded protein biomarkers to determine whether the combination of these markers was superior to any single marker. The cohort tested included 221 patients with resectable pancreatic ductal adenocarcinomas and 182 control patients without known cancer. mutations were detected in the plasma of 66 patients (30%), and every mutation found in the plasma was identical to that subsequently found in the patient's primary tumor (100% concordance). The use of in conjunction with four thresholded protein biomarkers increased the sensitivity to 64%. Only one of the 182 plasma samples from the control cohort was positive for any of the DNA or protein biomarkers (99.5% specificity). This combinatorial approach may prove useful for the earlier detection of many cancer types.
癌症的早期诊断是未来降低癌症死亡率的关键之一。在这里，我们描述了我们开发一种用于检测胰腺导管腺癌的非侵入性血液检测方法的努力。我们将基因突变的血液检测与经过仔细阈值处理的蛋白质生物标志物相结合，以确定这些标志物的组合是否优于任何单个标志物。所测试的队列包括 221 名可切除的胰腺导管腺癌患者和 182 名无已知癌症的对照患者。在 66 名患者（30%）的血浆中检测到了突变，并且在血浆中发现的每个突变都与随后在患者的原发性肿瘤中发现的突变相同（100%一致性）。使用与四个经过阈值处理的蛋白质生物标志物结合使用，将灵敏度提高到 64%。在对照组的 182 个血浆样本中，只有一个样本的任何 DNA 或蛋白质生物标志物呈阳性（99.5%特异性）。这种组合方法可能对许多癌症类型的早期检测很有用。
