Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers
Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers
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DOI：
10.1073/pnas.1704961114
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发表时间：
2017-09-19
影响因子：
11.1
通讯作者：
Lennon, Anne Marie
中科院分区：
文献类型：
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作者：
Cohen, Joshua D.;Javed, Ammar A.;Lennon, Anne Marie
癌症的早期诊断是未来减少癌症死亡的关键之一。在这里，我们描述了我们的努力，以开发一种无创血液检测胰腺导管腺癌。我们将KRAS基因突变的血液检测与仔细设定阈值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上级任何单一标志物。测试的队列包括221例可切除的胰腺导管腺癌患者和182例未患已知癌症的对照患者。在66名患者（30%）的血浆中检测到KRAS突变，并且在血浆中发现的每个突变与随后在患者的原发性肿瘤中发现的突变相同（100%一致性）。KRAS与四种阈值蛋白质生物标志物的结合使用将灵敏度提高到64%。来自对照组的182份血浆样本中仅1份对任何DNA或蛋白质生物标志物呈阳性（99.5%特异性）。这种组合方法可能被证明对许多癌症类型的早期检测有用。
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 KRAS 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. KRAS 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 KRAS 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.