Evidence map›Paper›PMID 33858496›Full record

ArticleClinical epigenetics2021

Identification of DNA methylation markers for early detection of CRC indicates a role for nervous system-related genes in CRC.

Glenn Rademakers, Maartje Massen, Alexander Koch, Muriel X Draht, Nikkie Buekers, Kim A D Wouters, Nathalie Vaes, Tim De Meyer, Beatriz Carvalho, Gerrit A Meijer and 4 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
5.1field-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.

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

16 citing papers in PubMed, 34 citations in OpenAlex.

  1. Epigenetics · 2026
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  10. miR-23a-3p promotes the development of colon cancer by inhibiting the expression of NDRG4.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Article
  11. Nerves in gastrointestinal cancer: from mechanism to modulations.Nature reviews. Gastroenterology & hepatology · 2022
    Review
  12. Article
  13. Article
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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

14 authors at 4 institutions in 3 countries.

Glenn Rademakers *Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Maartje Massen *Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Alexander Koch *Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Muriel X DrahtDepartment of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Nikkie BuekersDepartment of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Kim A D WoutersDepartment of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Nathalie VaesDepartment of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Tim De MeyerDepartment of Data Analysis and Mathematical Modelling, Ghent University, Ghent, Belgium.
Beatriz CarvalhoDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Gerrit A MeijerDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
James G HermanThe Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Kim M SmitsDepartment of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Manon van EngelandDepartment of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Veerle MelotteDepartment of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. veerle.melotte@maastrichtuniversity.nl.ORCID 0000-0002-9459-123X
Maastricht University Medical Centre · NLThe Netherlands Cancer Institute · NLGhent University · BEUPMC Hillman Cancer Center · US

Funding

KWF Kankerbestrijding UM-2-13-6075SU2C-DCS International Translational Cancer Research Dream Team Grant Stand Up To Cancer (SU2C)-AACR- DT1415, MEDOCC
6 · The paper itself

Abstract

purposeColonoscopy and the fecal immunochemical test (FIT) are currently the most widely used screening modalities for colorectal cancer (CRC), however, both with their own limitations. Here we aim to identify and validate stool-based DNA methylation markers for the early detection of CRC and investigate the biological pathways prone to DNA methylation.

methodsDNA methylation marker discovery was performed using The Cancer Genome Atlas (TCGA) colon adenocarcinoma data set consisting of normal and primary colon adenocarcinoma tissue. The performance of the five best candidate markers and a previously identified marker, NDRG4, was evaluated on tissues and whole stool samples of healthy subjects and CRC patients using quantitative MSP assays. The results were compared and combined with FIT data. Finally, pathway and gene ontology enrichment analyses were performed using ToppFun, GOrilla and clusterProfiler.

resultsGDNF, HAND2, SLC35F3, SNAP91 and SORCS1 were ranked as the best performing markers. Gene combinations of all five markers, NDRG4 and FIT were evaluated to establish the biomarker panel with the highest diagnostic potential, resulting in the identification of GDNF/SNAP91/NDRG4/FIT as the best performing marker panel. Pathway and gene ontology enrichment analyses revealed that genes associated with the nervous system were enriched in the set of best performing CRC-specific biomarkers.

conclusionIn silico discovery analysis using TCGA-derived data yielded a novel DNA-methylation-based assay for the early detection of CRC, potentially improving current screening modalities. Additionally, nervous system-related pathways were enriched in the identified genes, indicating an epigenetic regulation of neuronal genes in CRC.

Indexed as

AgedBiomarkers, TumorCentral Nervous SystemColorectal NeoplasmsDNA MethylationEarly Detection of CancerEpigenesis, GeneticEpigenomicsFemaleHumansMaleMiddle AgedPromoter Regions, GeneticReproducibility of ResultsSensitivity and SpecificityBiomarkers, TumorColorectal cancerDiagnostic markersDNA methylationIn silico discoveryNervous system

Identifiers

PMID33858496
PMCPMC8048074
OpenAlexW3153087755

What OpenQuestion holds

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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.