Evidence map›Paper›PMID 38123998›Full record

ArticleGut2024

Protein biomarkers and alternatively methylated cell-free DNA detect early stage pancreatic cancer.

Roni Ben-Ami, Qiao-Li Wang, Jinming Zhang, Julianna G Supplee, Johannes F Fahrmann, Roni Lehmann-Werman, Lauren K Brais, Jonathan Nowak, Chen Yuan, Maureen Loftus and 34 more

Open access · hybridAbstract read
In one paragraph

Article in Gut, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
7.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 34 citations in OpenAlex.

  1. A multi-analyte blood test for acute spinal cord injury.The Journal of clinical investigation · 2025
    Trial
  2. Review
  3. Coixenolide Enhances Antitumor Immunity of Cytotoxic CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Pancreatic cancer in 2025: Have we found a solution?World journal of gastroenterology · 2025
    Review
  16. Review
  17. ctDNA in Pancreatic Adenocarcinoma: A Critical Appraisal.Current oncology (Toronto, Ont.) · 2025
    Review
  18. Article
  19. Article
  20. Proteomics in pancreatic cancer.Biomarker research · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

44 authors at 11 institutions in 3 countries.

Roni Ben-AmiDepartment of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.ORCID 0000-0002-4939-0324
Qiao-Li WangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Jinming ZhangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Julianna G SuppleeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Johannes F FahrmannDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Roni Lehmann-WermanDepartment of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Lauren K BraisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Jonathan NowakDepartment of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.ORCID 0000-0002-0943-7407
Chen YuanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-0708-9648
Maureen LoftusDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Ana BabicDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Ehsan IrajizadDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Tal DavidiSharett Institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Aviad ZickSharett Institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Ayala HubertSharett Institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Daniel NeimanDepartment of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Sheina PiyanzinDepartment of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Ofer Gal-RosenbergDepartment of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Amit HornDepartment of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Ruth ShemerDepartment of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Benjamin GlaserDepartment of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Natalia BoosDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Kunal JajooDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Linda LeeDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Thomas E ClancyDepartment of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Douglas A RubinsonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Kimmie NgDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
John A ChabotDepartment of Surgery, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, USA.
Fay KastrinosDivision of Digestive and Liver Diseases, Columbia University Irving Medical Cancer and the Vagelos College of Physicians and Surgeons, New York, New York, USA.
Michael KlugerDepartment of Surgery, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, USA.
Andrew J AguirreDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Pasi A JänneDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Nabeel BardeesyMassachusetts General Hospital Cancer Center, Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
Ben StangerDepartment of Medicine, Division of Gastroenterology, Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Mark H O'HaraDepartment of Medicine, Division of Hematology-Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jacob TillDepartment of Medicine, Division of Hematology-Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Anirban MaitraDepartment of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Erica L CarpenterDepartment of Medicine, Division of Hematology-Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Andrea J BullockDivision of Hematology and Oncology, Beth-Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Jeanine GenkingerDepartment of epidemiology, Mailman school of public health, Columbia university, New York, New York, USA.
Samir M HanashDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cloud P PaweletzDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Yuval DorDepartment of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel Brian_Wolpin@dfci.harvard.edu yuvald@ekmd.huji.ac.il.
Brian M WolpinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA Brian_Wolpin@dfci.harvard.edu yuvald@ekmd.huji.ac.il.
Brigham and Women's Hospital · USHarvard University · USHebrew University of Jerusalem · ILThe University of Texas MD Anderson Cancer Center · USColumbia University Irving Medical Center · USHadassah Medical Center · ILUniversity of Pennsylvania · USBeth Israel Deaconess Medical Center · USCancer Research Institute · USColumbia University · USMassachusetts General Hospital · US

Funding

Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI MAYER, ROBERT J · 2007 to 2023
$33.2M
Project 3: Inhibiting Oxidative Phosphorylation in Pancreatic CancerP50CA221707 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KOPETZ, SCOTT, MAITRA, ANIRBAN · 2019 to 2023
$11.0M
Clinical Validation Center for Early Detection of Pancreatic CancerU01CA200468 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ANIRBAN MAITRA · 2016 to 2026
$11.0M
Circulating Biomarker Consortium for Pancreatic Cancer Early DetectionU01CA210171 · NCI · DANA-FARBER CANCER INST · PI Michael H. Rosenthal, Brian Matthew Wolpin · 2016 to 2026
$8.7M
Imaging and Molecular Correlates of Progression in Cystic Neoplasms of the PancreasU01CA196403 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MAITRA, ANIRBAN · 2015 to 2020
$5.8M
Early change in plasma tumor DNA as a patient and trial-level diagnostic in advanced lung cancerR01CA240592 · NCI · DANA-FARBER CANCER INST · PI PAWELETZ, CLOUD PETER · 2020 to 2024
$2.2M
Obesity and Pancreatic Cancer Progression and SurvivalK07CA222159 · NCI · DANA-FARBER CANCER INST · PI BABIC, ANA · 2018 to 2022
$747k
NCI NIH HHS K07 CA222159NCI NIH HHS P50 CA127003NCI NIH HHS P50 CA221707NCI NIH HHS R01 CA240592NCI NIH HHS U01 CA196403NCI NIH HHS U01 CA200468NCI NIH HHS U01 CA210171
6 · The paper itself

Abstract

objectivePancreatic 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.

designTo 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.

resultsComparative 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).

conclusionA combined panel of circulating markers including proteins and methylated cfDNA increased discrimination compared with CA19-9 alone for early stage PDAC.

Indexed as

AdenocarcinomaCarcinoma, Pancreatic DuctalCell-Free Nucleic AcidsPancreatic NeoplasmsBiomarkers, TumorCA-19-9 AntigenDNA MethylationHumansPancreasBiomarkers, TumorCA-19-9 AntigenCell-Free Nucleic AcidsMETHYLATIONPANCREATIC CANCERTUMOUR MARKERS

Identifiers

PMID38123998
PMCPMC10958271
OpenAlexW4389669597

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.