4 years ago

Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers [Medical Sciences]

Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers [Medical Sciences]
Lu Li, Martin A. Makary, Ralph H. Hruban, Christopher L. Wolfgang, Claudio Doglioni, Aatur D. Singhi, Matthew J. Weiss, Ammar A. Javed, Fay Wong, Cristian Tomasetti, Samir M. Hanash, Song Cheol Kim, Marco Dal Molin, Michael G. Goggins, Jin He, Yuxuan Wang, Jeanne Tie, Peter Gibbs, Joshua D. Cohen, Seung-Mo Hong, Gloria M. Petersen, Randall E. Brand, Peter J. Allen, Nickolas Papadopoulos, Christopher Thoburn, Massimo Falconi, Michele T. Yip-Schneider, Natalie Silliman, Bert Vogelstein, Lisa Dobbyn, Kenneth W. Kinzler, Janine Ptak, Anne Marie Lennon, Alison P. Klein, Maria Popoli, Nita Ahuja, Anirban Maitra, Joy Schaefer, Mark Schattner, C. Max Schmidt

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.

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