Evidence map›Paper›PMID 30953539›Full record

ArticleClinical epigenetics2019

Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood.

Maryam A L Eissa, Lane Lerner, Eihab Abdelfatah, Nakul Shankar, Joseph K Canner, Nesrin M Hasan, Vesal Yaghoobi, Barry Huang, Zachary Kerner, Felipe Takaesu and 12 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05495685 (Pancreatic Cancer Detection by Liquid Biopsy in Peripheral Blood), which is not on this map. Cited by 105 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 3 pooled it
8.4field-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.

NCT05495685 unknown statusnot on this mapstarted 2022, after this paper: background citation

Pancreatic Cancer Detection by Liquid Biopsy in Peripheral Blood: A Prospective Study

TypeobservationalSponsorChanghai HospitalRan2022 to 2024Enrolled450ConditionsCancer
3 · Its place in the literature

Who cites it

105 citing papers in PubMed, 3 syntheses or guidelines pooled it, 222 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Catching pancreatic cancer early: Are we there yet?Journal of the National Cancer Center · 2026
    Review
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  8. Article
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  12. Article
  13. Article
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  15. Article
  16. Challenges of early detection of pancreatic cancer.The Journal of clinical investigation · 2025
    Review
  17. Review
  18. Review
  19. Review
  20. Article

45 more citing papers are in PubMed but not listed here.

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

22 authors at 5 institutions in 1 country.

Maryam A L EissaDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lane LernerDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Eihab AbdelfatahDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nakul ShankarDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Joseph K CannerDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nesrin M HasanDepartment of Surgery, Yale-New Haven Health, Yale University, School of Medicine, P.O. Box 208062, New Haven, CT, 06520-8062, USA.
Vesal YaghoobiDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Barry HuangDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Zachary KernerDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Felipe TakaesuDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Christopher WolfgangDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ruby KwakDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael RuizDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Matthew TamDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Thomas R PisanicJohns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD, USA.
Christine A Iacobuzio-DonahueDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.
Ralph H HrubanDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jin HeDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tza-Huei WangJohns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD, USA.
Laura D WoodDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Anup SharmaDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nita AhujaDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. nita.ahuja@yale.edu.
Johns Hopkins University · USJohns Hopkins Medicine · USYale University · USCancer Research Center · USMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
(PQD3)Molecular Profiles associated with Long-Term Survival in pancreas CancerR01CA185357 · NCI · YALE UNIVERSITY · PI AHUJA, NITA, EASWARAN, HARIHARAN · 2014 to 2017
$1.8M
NCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA185357
6 · The paper itself

Abstract

backgroundDespite improvements in cancer management, most pancreatic cancers are still diagnosed at an advanced stage. We have recently identified promoter DNA methylation of the genes ADAMTS1 and BNC1 as potential blood biomarkers of pancreas cancer. In this study, we validate this biomarker panel in peripheral cell-free tumor DNA of patients with pancreatic cancer.

resultsSensitivity and specificity for each gene are as follows: ADAMTS1 87.2% and 95.8% (AUC = 0.91; 95% CI 0.71-0.86) and BNC1 64.1% and 93.7% (AUC = 0.79; 95% CI 0.63-0.78). When using methylation of either gene as a combination panel, sensitivity increases to 97.3% and specificity to 91.6% (AUC = 0.95; 95% CI 0.77-0.90). Adding pre-operative CA 19-9 values to the combined two-gene methylation panel did not improve sensitivity. Methylation of ADAMTS1 was found to be positive in 87.5% (7/8) of stage I, 77.8% (7/9) of stage IIA, and 90% (18/20) of stage IIB disease. Similarly, BNC1 was positive in 62.5% (5/8) of stage I patients, 55.6% (5/9) of stage IIA, and 65% (13/20) of patients with stage IIB disease. The two-gene panel (ADAMTS1 and/or BNC1) was positive in 100% (8/8) of stage I, 88.9% (8/9) of stage IIA, and 100% (20/20) of stage IIB disease. The sensitivity and specificity of the two-gene panel for localized pancreatic cancer (stages I and II), where the cancer is eligible for surgical resection with curative potential, was 94.8% and 91.6% respectively. Additionally, the two-gene panel exhibited an AUC of 0.95 (95% CI 0.90-0.98) compared to 57.1% for CA 19-9 alone.

conclusionThe methylation status of ADAMTS1 and BNC1 in cfDNA shows promise for detecting pancreatic cancer during the early stages when curative resection of the tumor is still possible. This minimally invasive blood-based biomarker panel could be used as a promising tool for diagnosis and screening in a select subset of high-risk populations.

Indexed as

DNA MethylationADAMTS1 ProteinBiomarkers, TumorCell-Free Nucleic AcidsDNA-Binding ProteinsEarly Detection of CancerEpigenesis, GeneticFemaleHumansMaleNeoplasm StagingPancreatic NeoplasmsPromoter Regions, GeneticSensitivity and SpecificityTranscription FactorsADAMTS1 ProteinADAMTS1 protein, humanBiomarkers, TumorBNC1 protein, humanCell-Free Nucleic AcidsDNA-Binding ProteinsTranscription FactorsADAMTS1BiomarkerBNC1Cell-free DNAMethylationMOBPancreatic cancer

Identifiers

PMID30953539
PMCPMC6451253
OpenAlexW2941174123

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Registered trials

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.