Protein biomarkers and alternatively methylated cell-free DNA detect early stage pancreatic cancer
Ben-Ami, Roni ; Wang, Qiao-Li LU
; Zhang, Jinming
; Supplee, Julianna G
; Fahrmann, Johannes F
; Lehmann-Werman, Roni
; Brais, Lauren K
; Nowak, Jonathan
; Yuan, Chen
and Loftus, Maureen
, et al.
(2024)
In Gut
73(4).
p.639-648
- Abstract
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage. Liquid biopsy approaches may facilitate detection of early stage PDAC when curative treatments can be employed.
DESIGN: To assess circulating marker discrimination in training, testing and validation patient cohorts (total n=426 patients), plasma markers were measured among PDAC cases and patients with chronic pancreatitis, colorectal cancer (CRC), and healthy controls. Using CA19-9 as an anchor marker, measurements were made of two protein markers (TIMP1, LRG1) and cell-free DNA (cfDNA) pancreas-specific methylation at 9 loci encompassing 61 CpG sites.
RESULTS: Comparative methylome analysis identified nine loci that were... (More)
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage. Liquid biopsy approaches may facilitate detection of early stage PDAC when curative treatments can be employed.
DESIGN: To assess circulating marker discrimination in training, testing and validation patient cohorts (total n=426 patients), plasma markers were measured among PDAC cases and patients with chronic pancreatitis, colorectal cancer (CRC), and healthy controls. Using CA19-9 as an anchor marker, measurements were made of two protein markers (TIMP1, LRG1) and cell-free DNA (cfDNA) pancreas-specific methylation at 9 loci encompassing 61 CpG sites.
RESULTS: Comparative methylome analysis identified nine loci that were differentially methylated in exocrine pancreas DNA. In the training set (n=124 patients), cfDNA methylation markers distinguished PDAC from healthy and CRC controls. In the testing set of 86 early stage PDAC and 86 matched healthy controls, CA19-9 had an area under the receiver operating characteristic curve (AUC) of 0.88 (95% CI 0.83 to 0.94), which was increased by adding TIMP1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.06), LRG1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02) or exocrine pancreas-specific cfDNA methylation markers at nine loci (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02). In the validation set of 40 early stage PDAC and 40 matched healthy controls, a combined panel including CA19-9, TIMP1 and a 9-loci cfDNA methylation panel had greater discrimination (AUC 0.86, 95% CI 0.77 to 0.95) than CA19-9 alone (AUC 0.82; 95% CI 0.72 to 0.92).
CONCLUSION: A combined panel of circulating markers including proteins and methylated cfDNA increased discrimination compared with CA19-9 alone for early stage PDAC.
(Less)
- author
- Ben-Ami, Roni
; Wang, Qiao-Li
LU
; Zhang, Jinming
; Supplee, Julianna G
; Fahrmann, Johannes F
; Lehmann-Werman, Roni
; Brais, Lauren K
; Nowak, Jonathan
; Yuan, Chen
and Loftus, Maureen
, et al. (More)
- Ben-Ami, Roni
; Wang, Qiao-Li
LU
; Zhang, Jinming
; Supplee, Julianna G
; Fahrmann, Johannes F
; Lehmann-Werman, Roni
; Brais, Lauren K
; Nowak, Jonathan
; Yuan, Chen
; Loftus, Maureen
; Babic, Ana
; Irajizad, Ehsan
; Davidi, Tal
; Zick, Aviad
; Hubert, Ayala
; Neiman, Daniel
; Piyanzin, Sheina
; Gal-Rosenberg, Ofer
; Horn, Amit
; Shemer, Ruth
; Glaser, Benjamin
; Boos, Natalia
; Jajoo, Kunal
; Lee, Linda
; Clancy, Thomas E
; Rubinson, Douglas A
; Ng, Kimmie
; Chabot, John A
; Kastrinos, Fay
; Kluger, Michael
; Aguirre, Andrew J
; Jänne, Pasi A
; Bardeesy, Nabeel
; Stanger, Ben
; O'Hara, Mark H
; Till, Jacob
; Maitra, Anirban
; Carpenter, Erica L
; Bullock, Andrea J
; Genkinger, Jeanine
; Hanash, Samir M
; Paweletz, Cloud P
; Dor, Yuval
and Wolpin, Brian M
(Less)
- publishing date
- 2024-03-07
- type
- Contribution to journal
- publication status
- published
- keywords
- Humans, CA-19-9 Antigen, Biomarkers, Tumor, Cell-Free Nucleic Acids/metabolism, Pancreatic Neoplasms/diagnosis, Carcinoma, Pancreatic Ductal/diagnosis, Pancreas/pathology, Adenocarcinoma/diagnosis, DNA Methylation
- in
- Gut
- volume
- 73
- issue
- 4
- pages
- 639 - 648
- publisher
- BMJ Publishing Group
- external identifiers
-
- scopus:85184706319
- pmid:38123998
- ISSN
- 1468-3288
- DOI
- 10.1136/gutjnl-2023-331074
- language
- English
- LU publication?
- no
- additional info
- © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.
- id
- f7b28cdf-9fc0-4a6d-a6af-b06a242d45eb
- date added to LUP
- 2025-05-12 17:13:53
- date last changed
- 2025-06-10 14:28:01
@article{f7b28cdf-9fc0-4a6d-a6af-b06a242d45eb,
abstract = {{<p>OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage. Liquid biopsy approaches may facilitate detection of early stage PDAC when curative treatments can be employed.</p><p>DESIGN: To assess circulating marker discrimination in training, testing and validation patient cohorts (total n=426 patients), plasma markers were measured among PDAC cases and patients with chronic pancreatitis, colorectal cancer (CRC), and healthy controls. Using CA19-9 as an anchor marker, measurements were made of two protein markers (TIMP1, LRG1) and cell-free DNA (cfDNA) pancreas-specific methylation at 9 loci encompassing 61 CpG sites.</p><p>RESULTS: Comparative methylome analysis identified nine loci that were differentially methylated in exocrine pancreas DNA. In the training set (n=124 patients), cfDNA methylation markers distinguished PDAC from healthy and CRC controls. In the testing set of 86 early stage PDAC and 86 matched healthy controls, CA19-9 had an area under the receiver operating characteristic curve (AUC) of 0.88 (95% CI 0.83 to 0.94), which was increased by adding TIMP1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.06), LRG1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02) or exocrine pancreas-specific cfDNA methylation markers at nine loci (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02). In the validation set of 40 early stage PDAC and 40 matched healthy controls, a combined panel including CA19-9, TIMP1 and a 9-loci cfDNA methylation panel had greater discrimination (AUC 0.86, 95% CI 0.77 to 0.95) than CA19-9 alone (AUC 0.82; 95% CI 0.72 to 0.92).</p><p>CONCLUSION: A combined panel of circulating markers including proteins and methylated cfDNA increased discrimination compared with CA19-9 alone for early stage PDAC.</p>}},
author = {{Ben-Ami, Roni and Wang, Qiao-Li and Zhang, Jinming and Supplee, Julianna G and Fahrmann, Johannes F and Lehmann-Werman, Roni and Brais, Lauren K and Nowak, Jonathan and Yuan, Chen and Loftus, Maureen and Babic, Ana and Irajizad, Ehsan and Davidi, Tal and Zick, Aviad and Hubert, Ayala and Neiman, Daniel and Piyanzin, Sheina and Gal-Rosenberg, Ofer and Horn, Amit and Shemer, Ruth and Glaser, Benjamin and Boos, Natalia and Jajoo, Kunal and Lee, Linda and Clancy, Thomas E and Rubinson, Douglas A and Ng, Kimmie and Chabot, John A and Kastrinos, Fay and Kluger, Michael and Aguirre, Andrew J and Jänne, Pasi A and Bardeesy, Nabeel and Stanger, Ben and O'Hara, Mark H and Till, Jacob and Maitra, Anirban and Carpenter, Erica L and Bullock, Andrea J and Genkinger, Jeanine and Hanash, Samir M and Paweletz, Cloud P and Dor, Yuval and Wolpin, Brian M}},
issn = {{1468-3288}},
keywords = {{Humans; CA-19-9 Antigen; Biomarkers, Tumor; Cell-Free Nucleic Acids/metabolism; Pancreatic Neoplasms/diagnosis; Carcinoma, Pancreatic Ductal/diagnosis; Pancreas/pathology; Adenocarcinoma/diagnosis; DNA Methylation}},
language = {{eng}},
month = {{03}},
number = {{4}},
pages = {{639--648}},
publisher = {{BMJ Publishing Group}},
series = {{Gut}},
title = {{Protein biomarkers and alternatively methylated cell-free DNA detect early stage pancreatic cancer}},
url = {{http://dx.doi.org/10.1136/gutjnl-2023-331074}},
doi = {{10.1136/gutjnl-2023-331074}},
volume = {{73}},
year = {{2024}},
}