Evidence map›Paper›PMID 31727158›Full record

ArticleClinical epigenetics2019

Novel DNA methylation biomarkers show high sensitivity and specificity for blood-based detection of colorectal cancer-a clinical biomarker discovery and validation study.

Sarah Østrup Jensen, Nadia Øgaard, Mai-Britt Worm Ørntoft, Mads Heilskov Rasmussen, Jesper Bertram Bramsen, Helle Kristensen, Peter Mouritzen, Mogens Rørbæk Madsen, Anders Husted Madsen, Kåre Gotschalck Sunesen and 5 more

Registry-linked trialOpen access · goldAbstract read
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 NCT06023004 (Circulating Tumor DNA Guided vs Opportunistic Colonoscopy Screening for CRC Detection After Acute Colonic Diverticulitis - the Diverticulitis Study), which is not on this map. Cited by 87 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 2 pooled it
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.

NCT06023004 active not recruitingnot on this mapstarted 2022, after this paper: background citation

Circulating Tumor DNA Guided vs Opportunistic Colonoscopy Screening for CRC Detection After Acute Colonic Diverticulitis - the Diverticulitis Study

TypeobservationalSponsorUniversity of AarhusRan2022 to 2030Enrolled250ConditionsColonic Diverticulitis, Colorectal Cancer, Acute Diverticulitis
3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 2 syntheses or guidelines pooled it, 142 citations in OpenAlex.

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  6. Circulating tumor DNA-guided response evaluation in patients with previously treated gastroesophageal adenocarcinoma.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026
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27 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

15 authors at 5 institutions in 1 country.

Sarah Østrup JensenDepartment of Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
Nadia ØgaardDepartment of Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
Mai-Britt Worm ØrntoftDepartment of Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
Mads Heilskov RasmussenDepartment of Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
Jesper Bertram BramsenDepartment of Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
Helle KristensenExiqon, Vedbæk, Denmark.
Peter MouritzenExiqon, Vedbæk, Denmark.
Mogens Rørbæk MadsenHerning Regional Hospital, Herning, Denmark.
Anders Husted MadsenHerning Regional Hospital, Herning, Denmark.
Kåre Gotschalck SunesenRanders Regional Hospital, Randers, Denmark.
Lene Hjerrild IversenDepartment of Surgery, Aarhus University Hospital, Aarhus, Denmark.
Søren LaurbergDepartment of Surgery, Aarhus University Hospital, Aarhus, Denmark.
Ib Jarle ChristensenCenter for Surgical Research, Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark.
Hans Jørgen NielsenCenter for Surgical Research, Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark.
Claus Lindbjerg AndersenDepartment of Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark. cla@clin.au.dk.ORCID 0000-0002-7406-2103
Aarhus University Hospital · DKRegionshospitalet Herning · DKHvidovre Hospital · DKRegional Hospital Randers · DKUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEarly detection plays an essential role to reduce colorectal cancer (CRC) mortality. While current screening methods suffer from poor compliance, liquid biopsy-based strategies for cancer detection is rapidly gaining promise. Here, we describe the development of TriMeth, a minimal-invasive blood-based test for detection of early-stage colorectal cancer. The test is based on assessment of three tumour-specific DNA methylation markers in circulating cell-free DNA.

resultsA thorough multi-step biomarker discovery study based on DNA methylation profiles of more than 5000 tumours and blood cell populations identified CRC-specific DNA methylation markers. The DNA methylation patterns of biomarker candidates were validated by bisulfite sequencing and methylation-specific droplet digital PCR in CRC tumour tissue and peripheral blood leucocytes. The three best performing markers were first applied to plasma from 113 primarily early-stage CRC patients and 87 age- and gender-matched colonoscopy-verified controls. Based on this, the test scoring algorithm was locked, and then TriMeth was validated in an independent cohort comprising 143 CRC patients and 91 controls. Three DNA methylation markers, C9orf50, KCNQ5, and CLIP4, were identified, each capable of discriminating plasma from colorectal cancer patients and healthy individuals (areas under the curve 0.86, 0.91, and 0.88). When combined in the TriMeth test, an average sensitivity of 85% (218/256) was observed (stage I: 80% (33/41), stage II: 85% (121/143), stage III: 89% (49/55), and stage IV: 88% (15/17)) at 99% (176/178) specificity in two independent plasma cohorts.

conclusionTriMeth enables detection of early-stage colorectal cancer with high sensitivity and specificity. The reported results underline the potential utility of DNA methylation-based detection of circulating tumour DNA in the clinical management of colorectal cancer.

Indexed as

DNA MethylationAgedAged, 80 and overBiomarkers, TumorCase-Control StudiesCirculating Tumor DNAColorectal NeoplasmsEarly Detection of CancerEpigenesis, GeneticFemaleHumansKCNQ Potassium ChannelsMaleMembrane ProteinsMiddle AgedSensitivity and SpecificityBiomarkers, TumorCirculating Tumor DNACLIP4 protein, humanKCNQ5 protein, humanKCNQ Potassium ChannelsMembrane ProteinsCancerCirculating tumour DNAColorectal cancerDNA methylationEarly detectionEpigenetic biomarkersLiquid biopsy

Identifiers

PMID31727158
PMCPMC6854894
OpenAlexW2983668961

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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.