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

被引：441

作者：

Cohen, Joshua D. ^{[1
,2
,3
,4
,5
]}

Javed, Ammar A. ^{[6
]}

Thoburn, Christopher ^{[3
]}

Wong, Fay ^{[1
,2
,3
,4
]}

Tie, Jeanne ^{[7
,8
,9
]}

Gibbs, Peter ^{[7
,8
,9
]}

Schmidt, C. Max ^{[10
,11
]}

Yip-Schneider, Michele T. ^{[10
]}

Allen, Peter J. ^{[12
]}

Schattner, Mark ^{[13
]}

Brand, Randall E. ^{[14
]}

Singhi, Aatur D. ^{[15
]}

Petersen, Gloria M. ^{[16
]}

Hong, Seung-Mo ^{[17
]}

Kim, Song Cheol ^{[18
]}

Falconi, Massimo ^{[19
]}

Doglioni, Claudio ^{[20
]}

Weiss, Matthew J. ^{[6
]}

Ahuja, Nita ^{[6
]}

He, Jin ^{[6
]}

Makary, Martin A. ^{[6
]}

Maitra, Anirban ^{[21
]}

Hanash, Samir M. ^{[21
]}

Dal Molin, Marco ^{[4
]}

Wang, Yuxuan ^{[1
,2
,3
,4
]}

Li, Lu ^{[22
]}

Ptak, Janine ^{[1
,2
,3
,4
]}

Dobbyn, Lisa ^{[1
,2
,3
,4
]}

Schaefer, Joy ^{[1
,2
,3
,4
]}

Silliman, Natalie ^{[1
,2
,3
,4
]}

Popoli, Maria ^{[1
,2
,3
,4
]}

Goggins, Michael G. ^{[3
,4
,23
,24
]}

Hruban, Ralph H. ^{[3
,4
,24
]}

Wolfgang, Christopher L. ^{[6
]}

Klein, Alison P. ^{[3
,4
,25
]}

Tomasetti, Cristian ^{[3
,22
,26
]}

Papadopoulos, Nickolas ^{[1
,2
,3
,4
]}

Kinzler, Kenneth W. ^{[1
,2
,3
,4
]}

Vogelstein, Bert ^{[2
,3
,4
]}

Lennon, Anne Marie ^{[1
,4
,23
]}

机构：

[1] Johns Hopkins Med Inst, Ludwig Ctr, Baltimore, MD 21287 USA

[2] Johns Hopkins Med Inst, Howard Hughes Med Inst, Baltimore, MD 21287 USA

[3] Johns Hopkins Med Inst, Sidney Kimmel Canc Ctr Johns Hopkins, Baltimore, MD 21287 USA

[4] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21287 USA

[5] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA

[6] Johns Hopkins Med Inst, Dept Surg, Baltimore, MD 21287 USA

[7] Walter & Eliza Hall Inst Med Res, Div Syst Biol & Personalized Med, Parkville, Vic 3021, Australia

[8] Univ Melbourne, Fac Med Dent & Hlth Sci, Melbourne, Vic 3010, Australia

[9] Western Hlth, Dept Med Oncol, Melbourne, Vic 3021, Australia

[10] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA

[11] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA

[12] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA

[13] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

[14] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA

[15] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15260 USA

[16] Mayo Clin, Dept Epidemiol, Rochester, MN 55902 USA

[17] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul 05505, South Korea

[18] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Hepatobiliary & Pancreas Surg, Seoul 05505, South Korea

[19] San Raffaele Sci Inst Res Hosp, Dept Surg, Div Pancreat Surg, I-20132 Milan, Italy

[20] San Raffaele Sci Inst Res Hosp, Dept Pathol, I-20132 Milan, Italy

[21] Univ Texas MD Anderson Canc Ctr, Sheikh Ahmed Ctr Pancreat Canc Res, Houston, TX 77030 USA

[22] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA

[23] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21287 USA

[24] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA

[25] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA

[26] Johns Hopkins Med Inst, Dept Oncol, Div Biostat & Bioinformat, Baltimore, MD 21287 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2017年 / 114卷 / 38期

基金：

英国医学研究理事会;

关键词：

early cancer detection; liquid biopsy; circulating tumor DNA; protein biomarkers; pancreatic cancer; CLINICOPATHOLOGICAL ASPECTS; CLONAL HEMATOPOIESIS; MARKERS; MUTATIONS; FLUOROURACIL; OSTEOPONTIN; EXPRESSION; CARCINOMA; DIAGNOSIS; RECEPTOR;

D O I：

10.1073/pnas.1704961114

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：10202 / 10207

页数：6

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