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 He; Martin 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

doi:10.1073/pnas.1704961114

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

Quantitative Health Sciences

Research output: Contribution to journal › Article › peer-review

228 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 language	English (US)
Pages (from-to)	10202-10207
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Issue number	38
DOIs	https://doi.org/10.1073/pnas.1704961114
State	Published - 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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10.1073/pnas.1704961114

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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

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 et al.
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 journal › Article › peer-review

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 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

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

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{\textquoteright}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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AU - Cohen, Joshua D.

AU - Javed, Ammar A.

AU - Thoburn, Christopher

AU - Wong, Fay

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 G.

AU - Hruban, Ralph H.

AU - Wolfgang, Christopher L.

AU - Klein, Alison P.

AU - Tomasetti, Cristian

AU - Papadopoulos, Nickolas

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Lennon, Anne Marie

PY - 2017/9/19

Y1 - 2017/9/19

N2 - 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.

AB - 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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KW - Early cancer detection

KW - Liquid biopsy

KW - Pancreatic cancer

KW - Protein biomarkers

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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

Abstract

Keywords

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