Evidence map›Paper›PMID 40241172›Full record

ArticleBMC biology2025

Colorectal cancer progression to metastasis is associated with dynamic genome-wide biphasic 5-hydroxymethylcytosine accumulation.

Ben Murcott, Floris Honig, Dominic Oliver Halliwell, Yuan Tian, James Lawrence Robson, Piotr Manasterski, Jennifer Pinnell, Thérèse Dix-Peek, Santiago Uribe-Lewis, Ashraf E K Ibrahim and 4 more

Abstract read
In one paragraph

Article in BMC biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Cell identity and 5-hydroxymethylcytosine.Epigenetics & chromatin · 2025
    Review
  5. Article
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.

Ben MurcottDepartment of Life Sciences, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Floris HonigDepartment of Life Sciences, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Dominic Oliver HalliwellDepartment of Life Sciences, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Yuan TianDepartment of Life Sciences, University of Bath, Claverton Down, Bath, BA2 7AY, UK.ORCID http://orcid.org/0000-0003-1312-6166
James Lawrence RobsonDepartment of Applied Sciences, University of the West of England, Bristol, BS16 1QY, UK.ORCID http://orcid.org/0000-0003-0157-1692
Piotr ManasterskiEdinburgh Cancer Research Centre, Institute of Genetics and Cancer, The University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK.
Jennifer PinnellPublic Library of Science, Nine Hills Road, Cambridge, CB2 1GE, UK.
Thérèse Dix-PeekDepartment of Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Johannesburg, 2193, South Africa.
Santiago Uribe-LewisThe Stokes Center for Urology, Royal Surrey Hospital NHS Foundation Trust, Guildford, GU2 7XX, UK.
Ashraf E K IbrahimNorth West Anglia Foundation Trust, Peterborough City Hospital, Bretton Gate, Peterborough, PE3 9GZ, UK.
Julia SeroDepartment of Life Sciences, Centre for Bioengineering & Biomedical Technologies, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
David GurevichDepartment of Life Sciences, Centre for Bioengineering & Biomedical Technologies, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Nikolas NikolaouClinical and Biomedical Sciences, Living Systems Institute, University of Exeter, Exeter, EX4 4QD, UK.
Adele MurrellDepartment of Life Sciences, Centre for Bioengineering & Biomedical Technologies, Centre for Mathematical Biology, University of Bath, Claverton Down, Bath, BA2 7AY, UK. amm95@bath.ac.uk.

Funding

Biotechnology and Biological Sciences Research Council 2598658Cancer Research UK (CRUK SEB-Institute Group Award A ref10182Engineering and Physical Sciences Research Council Engineering and Physical Research CouncilMedical Research Council MR/P000711/1Medical Research Council MRT000481/1Wellcome TrustWellcome Trust Sir Henry Dale fellowship 220188/A/20/Z.
6 · The paper itself

Abstract

backgroundColorectal cancer (CRC) progression from adenoma to adenocarcinoma is associated with global reduction in 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). DNA hypomethylation continues upon liver metastasis. Here we examine 5hmC changes upon progression to liver metastasis.

results5hmC is increased in metastatic liver tissue relative to the primary colon tumour and expression of TET2 and TET3 is negatively correlated with risk for metastasis in patients with CRC. Genes associated with increased 5-hydroxymethylcytosine show KEGG enrichment for adherens junctions, cytoskeleton and cell migration around a core cadherin (CDH2) network. Overall, the 5-hydroxymethylcyosine profile in the liver metastasis is similar to normal colon appearing to recover at many loci where it was originally present in normal colon and then spreading to adjacent sites. The underlying sequences at the recover and spread regions are enriched for SALL4, ZNF770, ZNF121 and PAX5 transcription factor binding sites. Finally, we show in a zebrafish migration assay using SW480 CRISPR-engineered TET knockout and rescue cells that reduced TET expression leads to a reduced migration frequency.

conclusionsTogether these results suggest a biphasic trajectory for 5-hydroxymethyation dynamics that has bearing on potential therapeutic interventions aimed at manipulating 5-hydroxymethylcytosine levels.

Indexed as

5-MethylcytosineColorectal NeoplasmsCytosineLiver NeoplasmsAnimalsCell Line, TumorDioxygenasesDisease ProgressionDNA-Binding ProteinsDNA MethylationGene Expression Regulation, NeoplasticHumansNeoplasm MetastasisProto-Oncogene ProteinsZebrafish5-hydroxymethylcytosine5-MethylcytosineCytosineDioxygenasesDNA-Binding ProteinsProto-Oncogene ProteinsTET2 protein, human5-HydroxymethylcytosineColorectal cancer progression to metastasisEpigeneticsTen-eleven-translocation (TET)Zebrafish assay

Identifiers

PMID40241172
PMCPMC12004686

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.