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

Author:

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

Abstract

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 forKRASgene 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.KRASmutations 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 ofKRASin 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.

Funder

Lustgarten Foundation

Virginia and D.K. Ludwig Fund for Cancer Research

HHS | National Institutes of Health

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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