Evidence map›Paper›PMID 34465601›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021

EpiPanGI Dx: A Cell-free DNA Methylation Fingerprint for the Early Detection of Gastrointestinal Cancers.

Raju Kandimalla, Jianfeng Xu, Alexander Link, Takatoshi Matsuyama, Kensuke Yamamura, M Iqbal Parker, Hiroyuki Uetake, Francesc Balaguer, Erkut Borazanci, Susan Tsai and 7 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06476067 (Predicting Postoperative Early Tumor Recurrence in Patients With Esophageal Squamous Cell Carcinoma), which is not on this map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 4% 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.

NCT06476067 recruitingnot on this map

Predicting Postoperative Early Tumor Recurrence in Patients With Esophageal Squamous Cell Carcinoma

TypeobservationalSponsorCity of Hope Medical CenterRan2006 to 2028Enrolled150ConditionsEsophageal Cancer, Recurrence, DNA MethylationArmsSurgery
3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
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  9. Novel Liquid Biopsy in Gastrointestinal Cancers.Journal of gastroenterology and hepatology · 2026
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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

17 authors at 12 institutions in 5 countries.

Raju Kandimalla *Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute, Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas.ORCID 0000-0002-0342-5229
Jianfeng Xu *Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.ORCID 0000-0001-5592-3265
Alexander LinkDepartment of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.ORCID 0000-0002-9514-4562
Takatoshi MatsuyamaDepartment of Gastrointestinal Surgery, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan.
Kensuke YamamuraDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
M Iqbal ParkerDivision of Medical Biochemistry and Structural Biology, Institute for Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0001-7087-3825
Hiroyuki UetakeDepartment of Specialized Surgery, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan.
Francesc BalaguerGastroenterology Department, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Clínic, University of Barcelona, Barcelona, Spain.
Erkut BorazanciHonorHealth Research Institute, Scottsdale, Arizona.ORCID 0000-0001-5136-5462
Susan TsaiDepartment of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin.
Douglas EvansDepartment of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin.ORCID 0000-0001-5708-467X
Stephen J MeltzerDepartment of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Hideo BabaDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Randall BrandDepartment of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania.ORCID 0000-0002-4136-3313
Daniel Von HoffHonorHealth Research Institute, Scottsdale, Arizona.ORCID 0000-0003-4723-7681
Wei Li *Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas. ajgoel@coh.org wei.li@uci.edu.
Ajay Goel *Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute, Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas. ajgoel@coh.org wei.li@uci.edu.
Baylor College of Medicine · USBaylor University Medical Center · USKumamoto University · JPMedical College of Wisconsin · USTokyo Medical and Dental University · JPCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESHonorHealth · USJohns Hopkins University · USOtto-von-Guericke-Universität Magdeburg · DETranslational Genomics Research Institute · USUniversity of Cape Town · ZAUniversity of Pittsburgh · US

Funding

Noncoding RNA Biomarkers for Noninvasive and Early Detection of Pancreatic CancerU01CA214254 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Ajay Goel, DANIEL D VON HOFF · 2017 to 2026
$8.9M
The Biology and Diagnosis of HNPCCR01CA072851 · NCI · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI GOEL, AJAY · 1996 to 2019
$6.6M
Academic-Industrial Partnership for Non-invasive Barrett's Esophagus DetectionR01DK118250 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI MELTZER, STEPHEN J · 2018 to 2022
$3.8M
Computational and Experimental Modeling of Alternative PolyadenylationR01CA193466 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LI, WEI · 2016 to 2025
$3.3M
Transfer: DNA Methylation Canyons in Human Cancers: Methods, Target Genes and Functional ConsequencesR01CA228140 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LI, WEI · 2019 to 2023
$2.8M
Facile screening for esophageal cancer in LMICsUH3CA211457 · NCI · JOHNS HOPKINS UNIVERSITY · PI MELTZER, STEPHEN J, WANG, TZA-HUEI JEFF · 2019 to 2021
$2.8M
Aspirin and Cancer Prevention in Lynch Syndrome: From Cell to Population DataU01CA187956 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI GOEL, AJAY, WODARZ, DOMINIK F · 2014 to 2018
$2.7M
Computational and Experimental Modeling of Epigenetic DNA MethylationR01HG007538 · NHGRI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LI, WEI · 2014 to 2018
$1.9M
MicroRNA Biomarkers for Determining Treatment Response in Colorectal CancerR01CA202797 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI GOEL, AJAY · 2016 to 2020
$1.9M
Development of microRNA Biomarkers For Noninvasive Detection of Colorectal CancerR01CA184792 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI GOEL, AJAY · 2015 to 2019
$1.8M
METHYLATION BIOMARKER DEVELOPMENT FOR NONINVASIVE DETECTION OF COLORECTAL CANCERR01CA181572 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI GOEL, AJAY · 2014 to 2018
$1.6M
Facile screening for esophageal cancer in LMICsUG3CA211457 · NCI · JOHNS HOPKINS UNIVERSITY · PI MELTZER, STEPHEN J, WANG, TZA-HUEI JEFF · 2017 to 2018
$861k
Medical Research Council MC_PC_16097NCI NIH HHS R01 CA072851NCI NIH HHS R01 CA181572NCI NIH HHS R01 CA184792NCI NIH HHS R01 CA193466NCI NIH HHS R01 CA202797NCI NIH HHS R01 CA228140NCI NIH HHS U01 CA187956NCI NIH HHS U01 CA214254NCI NIH HHS UG3 CA211457NCI NIH HHS UH3 CA211457NHGRI NIH HHS R01 HG007538NIDDK NIH HHS R01 DK118250
6 · The paper itself

Abstract

purposeDNA methylation alterations have emerged as front-runners in cell-free DNA (cfDNA) biomarker development. However, much effort to date has focused on single cancers. In this context, gastrointestinal (GI) cancers constitute the second leading cause of cancer-related deaths worldwide; yet there is no blood-based assay for the early detection and population screening of GI cancers. EXPERIMENTAL

designHerein, we performed a genome-wide DNA methylation analysis of multiple GI cancers to develop a pan-GI diagnostic assay. By analyzing DNA methylation data from 1,781 tumor and adjacent normal tissues, we first identified differentially methylated regions (DMR) between individual GI cancers and adjacent normal, as well as across GI cancers. We next prioritized a list of 67,832 tissue DMRs by incorporating all significant DMRs across various GI cancers to design a custom, targeted bisulfite sequencing platform. We subsequently validated these tissue-specific DMRs in 300 cfDNA specimens and applied machine learning algorithms to develop three distinct categories of DMR panels

resultsWe identified three distinct DMR panels: (i) cancer-specific biomarker panels with AUC values of 0.98 (colorectal cancer), 0.98 (hepatocellular carcinoma), 0.94 (esophageal squamous cell carcinoma), 0.90 (gastric cancer), 0.90 (esophageal adenocarcinoma), and 0.85 (pancreatic ductal adenocarcinoma); (ii) a pan-GI panel that detected all GI cancers with an AUC of 0.88; and (iii) a multi-cancer (tissue of origin) prediction panel, EpiPanGI Dx, with a prediction accuracy of 0.85-0.95 for most GI cancers.

conclusionsUsing a novel biomarker discovery approach, we provide the first evidence for a cfDNA methylation assay that offers robust diagnostic accuracy for GI cancers.

Indexed as

Biomarkers, TumorCell-Free Nucleic AcidsDNA MethylationArea Under CurveEarly Detection of CancerEpigenesis, GeneticEpigenomicsGastrointestinal NeoplasmsGene Expression ProfilingHumansROC CurveBiomarkers, TumorCell-Free Nucleic Acids

Identifiers

PMID34465601
PMCPMC8595812
OpenAlexW3196756026

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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.