Medline ® Abstract for Reference 99
of 'Molecular pathogenesis of exocrine pancreatic cancer'
Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers.
Cohen JD, Javed AA, Thoburn C, Wong F, Tie J, Gibbs P, Schmidt CM, Yip-Schneider MT, Allen PJ, Schattner M, Brand RE, Singhi AD, Petersen GM, Hong SM, Kim SC, Falconi M, Doglioni C, Weiss MJ, Ahuja N, He J, Makary MA, Maitra A, Hanash SM, Dal Molin M, Wang Y, Li L, Ptak J, Dobbyn L, Schaefer J, Silliman N, Popoli M, Goggins MG, Hruban RH, Wolfgang CL, Klein AP, Tomasetti C, Papadopoulos N, Kinzler KW, Vogelstein B, Lennon AM
Proc Natl Acad Sci U S A. 2017;114(38):10202. 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 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 mayprove useful for the earlier detection of many cancer types.
The Ludwig Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287.