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

Publication ,  Journal Article
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 ...
Published in: Proc Natl Acad Sci U S A
September 19, 2017

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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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

September 19, 2017

Volume

114

Issue

38

Start / End Page

10202 / 10207

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins p21(ras)
  • Pancreatic Neoplasms
  • Middle Aged
  • Male
  • Liquid Biopsy
  • Humans
  • Genes, p53
  • Female
  • Circulating Tumor DNA
  • Case-Control Studies
 

Citation

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Cohen, J. D., Javed, A. A., Thoburn, C., Wong, F., Tie, J., Gibbs, P., … Lennon, A. M. (2017). Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. Proc Natl Acad Sci U S A, 114(38), 10202–10207. https://doi.org/10.1073/pnas.1704961114
Cohen, Joshua D., Ammar A. Javed, Christopher Thoburn, Fay Wong, Jeanne Tie, Peter Gibbs, C Max Schmidt, et al. “Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers.Proc Natl Acad Sci U S A 114, no. 38 (September 19, 2017): 10202–7. https://doi.org/10.1073/pnas.1704961114.
Cohen JD, Javed AA, Thoburn C, Wong F, Tie J, Gibbs P, et al. Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10202–7.
Cohen, Joshua D., et al. “Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers.Proc Natl Acad Sci U S A, vol. 114, no. 38, Sept. 2017, pp. 10202–07. Pubmed, doi:10.1073/pnas.1704961114.
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 S-M, 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. Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10202–10207.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

September 19, 2017

Volume

114

Issue

38

Start / End Page

10202 / 10207

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins p21(ras)
  • Pancreatic Neoplasms
  • Middle Aged
  • Male
  • Liquid Biopsy
  • Humans
  • Genes, p53
  • Female
  • Circulating Tumor DNA
  • Case-Control Studies