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

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

Research output: Contribution to journalArticle

151 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)10202-10207
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number38
DOIs
StatePublished - Sep 19 2017

Keywords

  • Circulating tumor DNA
  • Early cancer detection
  • Liquid biopsy
  • Pancreatic cancer
  • Protein biomarkers

ASJC Scopus subject areas

  • General

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    Cohen, J. D., Javed, A. A., Thoburn, C., Wong, F., Tie, J., Gibbs, P., Schmidt, C. M., Yip-Schneider, M. T., Allen, P. J., Schattner, M., Brand, R. E., Singhi, A. D., Petersen, G. M., Hong, S. M., Kim, S. C., Falconi, M., Doglioni, C., Weiss, M. J., Ahuja, N., ... Lennon, A. M. (2017). Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. Proceedings of the National Academy of Sciences of the United States of America, 114(38), 10202-10207. https://doi.org/10.1073/pnas.1704961114