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 S Goggins, Ralph H Hruban, Christopher Wolfgang, Alison Klein, Cristian Tomasetti, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Anne Marie O'Broin-Lennon

Research output: Contribution to journalArticle

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

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Pancreatic Neoplasms
Early Detection of Cancer
Biomarkers
Biopsy
DNA
Hematologic Tests
Mutation
Neoplasms
Proteins
Adenocarcinoma
Genes

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. / 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 S; Hruban, Ralph H; Wolfgang, Christopher; Klein, Alison; Tomasetti, Cristian; Papadopoulos, Nickolas; Kinzler, Kenneth W; Vogelstein, Bert; O'Broin-Lennon, Anne Marie.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 38, 19.09.2017, p. 10202-10207.

Research output: Contribution to journalArticle

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, MS, Hruban, RH, Wolfgang, C, Klein, A, Tomasetti, C, Papadopoulos, N, Kinzler, KW, Vogelstein, B & O'Broin-Lennon, AM 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, vol. 114, no. 38, pp. 10202-10207. https://doi.org/10.1073/pnas.1704961114
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 S ; Hruban, Ralph H ; Wolfgang, Christopher ; Klein, Alison ; Tomasetti, Cristian ; Papadopoulos, Nickolas ; Kinzler, Kenneth W ; Vogelstein, Bert ; O'Broin-Lennon, Anne Marie. / Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 38. pp. 10202-10207.
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AU - Javed, Ammar A.

AU - Thoburn, Christopher

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AU - Tie, Jeanne

AU - Gibbs, Peter

AU - Schmidt, C. Max

AU - Yip-Schneider, Michele T.

AU - Allen, Peter J.

AU - Schattner, Mark

AU - Brand, Randall E.

AU - Singhi, Aatur D.

AU - Petersen, Gloria M.

AU - Hong, Seung Mo

AU - Kim, Song Cheol

AU - Falconi, Massimo

AU - Doglioni, Claudio

AU - Weiss, Matthew J

AU - Ahuja, Nita

AU - He, Jin

AU - Makary, Martin A

AU - Maitra, Anirban

AU - Hanash, Samir M.

AU - Dal Molin, Marco

AU - Wang, Yuxuan

AU - Li, Lu

AU - Ptak, Janine

AU - Dobbyn, Lisa

AU - Schaefer, Joy

AU - Silliman, Natalie

AU - Popoli, Maria

AU - Goggins, Michael S

AU - Hruban, Ralph H

AU - Wolfgang, Christopher

AU - Klein, Alison

AU - Tomasetti, Cristian

AU - Papadopoulos, Nickolas

AU - Kinzler, Kenneth W

AU - Vogelstein, Bert

AU - O'Broin-Lennon, Anne Marie

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