Evidence map›Paper›PMID 26023084›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015

New DNA Methylation Markers for Pancreatic Cancer: Discovery, Tissue Validation, and Pilot Testing in Pancreatic Juice.

John B Kisiel, Massimo Raimondo, William R Taylor, Tracy C Yab, Douglas W Mahoney, Zhifu Sun, Sumit Middha, Saurabh Baheti, Hongzhi Zou, Thomas C Smyrk and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
6.0field-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

91 citing papers in PubMed, 129 citations in OpenAlex.

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  8. Multimodal Pancreatic Cancer Detection Using Methylated DNA Biomarkers in Pancreatic Juice and Plasma CA 19-9: A Prospective Multicenter Study.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2025
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  13. Early detection of pancreatic cancer: Study design and analytical considerations in biomarker discovery and early phase validation studies.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2024
    Review
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31 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

13 authors at 2 institutions in 1 country.

John B KisielDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Kisiel.john@mayo.edu.
Massimo RaimondoDivision of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.
William R TaylorDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Tracy C YabDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Douglas W MahoneyDepartment of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Zhifu SunDepartment of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Sumit MiddhaDepartment of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Saurabh BahetiDepartment of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Hongzhi ZouCenter for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.
Thomas C SmyrkAnatomic Pathology, Mayo Clinic, Rochester, Minnesota.
Lisa A BoardmanDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Gloria M PetersenDepartment of Epidemiology, Mayo Clinic, Rochester, Minnesota.
David A AhlquistDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Mayo Clinic · USJacksonville College · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
Tissue CoreP50CA102701 · NCI · MAYO CLINIC ROCHESTER · PI PETERSEN, GLORIA M. · 2004 to 2018
$32.7M
PILOT AND FEASIBILTY PROGRAMP30DK084567 · NIDDK · MAYO CLINIC ROCHESTER · PI GREGORY J. GORES · 2009 to 2026
$22.2M
Paul Calabresi Program in Clinical/Translational Research at Mayo ClinicK12CA090628 · NCI · MAYO CLINIC ROCHESTER · PI WEROHA, SARAVUT · 2001 to 2025
$19.7M
NCI NIH HHS CA90628NCI NIH HHS K12 CA090628NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA102701NIDDK NIH HHS P30 DK084567NIDDK NIH HHS P30DK084567
6 · The paper itself

Abstract

purposeDiscriminant markers for pancreatic cancer detection are needed. We sought to identify and validate methylated DNA markers for pancreatic cancer using next-generation sequencing unbiased by known targets. EXPERIMENTAL

designAt a referral center, we conducted four sequential case-control studies: discovery, technical validation, biologic validation, and clinical piloting. Candidate markers were identified using variance-inflated logistic regression on reduced-representation bisulfite DNA sequencing results from matched pancreatic cancers, benign pancreas, and normal colon tissues. Markers were validated technically on replicate discovery study DNA and biologically on independent, matched, blinded tissues by methylation-specific PCR. Clinical testing of six methylation candidates and mutant KRAS was performed on secretin-stimulated pancreatic juice samples from 61 patients with pancreatic cancer, 22 with chronic pancreatitis, and 19 with normal pancreas on endoscopic ultrasound. Areas under receiver-operating characteristics curves (AUC) for markers were calculated.

resultsSequencing identified >500 differentially hyper-methylated regions. On independent tissues, AUC on 19 selected markers ranged between 0.73 and 0.97. Pancreatic juice AUC values for CD1D, KCNK12, CLEC11A, NDRG4, IKZF1, PKRCB, and KRAS were 0.92*, 0.88, 0.85, 0.85, 0.84, 0.83, and 0.75, respectively, for pancreatic cancer compared with normal pancreas and 0.92*, 0.73, 0.76, 0.85*, 0.73, 0.77, and 0.62 for pancreatic cancer compared with chronic pancreatitis (*, P = 0.001 vs. KRAS).

conclusionsWe identified and validated novel DNA methylation markers strongly associated with pancreatic cancer. On pilot testing in pancreatic juice, best markers (especially CD1D) highly discriminated pancreatic cases from controls.

Indexed as

Biomarkers, TumorDNA MethylationAgedArea Under CurveCase-Control StudiesCpG IslandsEpigenesis, GeneticEpigenomicsFemaleGene DosageHumansMaleMiddle AgedNeoplasm StagingPancreatic JuicePancreatic NeoplasmsBiomarkers, Tumor

Identifiers

PMID26023084
PMCPMC4592385
OpenAlexW2099601545

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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.