Evidence map›Paper›PMID 28700744›Full record

ArticlePloS one2017

Hypermethylated DNA, a circulating biomarker for colorectal cancer detection.

Simon Ladefoged Rasmussen, Henrik Bygum Krarup, Kåre Gotschalck Sunesen, Martin Berg Johansen, Mogens Tornby Stender, Inge Søkilde Pedersen, Poul Henning Madsen, Ole Thorlacius-Ussing

Abstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 4 pooled it
–field-weighted citation impact
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

57 citing papers in PubMed, 4 syntheses or guidelines pooled it.

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  12. Methylation ofAdvanced biomedical research · 2025
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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

8 authors.

Simon Ladefoged RasmussenDepartment of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark.ORCID http://orcid.org/0000-0002-2560-4877
Henrik Bygum KrarupClinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
Kåre Gotschalck SunesenDepartment of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark.
Martin Berg JohansenUnit of Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark.
Mogens Tornby StenderDepartment of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark.
Inge Søkilde PedersenClinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
Poul Henning MadsenClinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
Ole Thorlacius-UssingDepartment of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundColorectal cancer (CRC) is one of the most common cancers in the western world. Screening is an efficient method of reducing cancer-related mortality. Molecular biomarkers for cancer in general and CRC in particular have been proposed, and hypermethylated DNA from stool or blood samples are already implemented as biomarkers for CRC screening. We aimed to evaluate the performance of proven hypermethylated DNA promoter regions as plasma based biomarkers for CRC detection.

methodsWe conducted a cross-sectional case-control study of 193 CRC patients and 102 colonoscopy-verified healthy controls. Using methylation specific polymerase chain reaction, we evaluated 30 DNA promoter regions previously found to be CRC specific. We used multivariable logistic regression with stepwise backwards selection, and subsequent leave-pair-out cross validation, to calculate the optimism corrected area under the receiver operating characteristics curve (AUC) for all stage as well as early stage CRC.

resultsNone of the individual DNA promoter regions provided an overall sensitivity above 30% at a reasonable specificity. However, seven hypermethylated promoter regions (ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, and VIM) along with the covariates sex and age yielded an optimism corrected AUC of 0.86 for all stage CRC and 0.85 for early stage CRC. Overall sensitivity for CRC detection was 90.7% at 72.5% specificity using a cut point value of 0.5.

conclusionsIndividual hypermethylated DNA promoter regions have limited value as CRC screening markers. However, a panel of seven hypermethylated promoter regions show great promise as a model for CRC detection.

Indexed as

AgedBiomarkers, TumorBone Morphogenetic Protein 3Case-Control StudiesColorectal NeoplasmsC-Reactive ProteinCross-Sectional StudiesDNA-Binding ProteinsDNA MethylationFemaleGene Expression Regulation, NeoplasticHumansLogistic ModelsMaleMiddle AgedNerve Tissue ProteinsALX4 protein, humanBiomarkers, TumorBMP3 protein, humanBone Morphogenetic Protein 3C-Reactive ProteinDNA-Binding ProteinsNerve Tissue ProteinsPentraxinsReceptors, Retinoic Acidretinoic acid receptor betaSDC2 protein, humanSyndecan-2Transcription Factors

Identifiers

PMID28700744
PMCPMC5507256

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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.