Evidence map›Paper›PMID 41559405›Full record

ArticleCommunications medicine2026

5-methylcytosine and 5-hydroxymethylcytosine are synergistic biomarkers for early detection of colorectal cancer.

Fabio Puddu, Annelie Johansson, Aurélie Modat, Jamie Scotcher, Riccha Sethi, Shirong Yu, Nick Harding, Mark Hill, Ermira Lleshi, Casper Lumby and 7 more

Abstract read
In one paragraph

Article in Communications medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
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.

Fabio Puddubiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.ORCID http://orcid.org/0000-0002-2033-5209
Annelie Johanssonbiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.
Aurélie Modatbiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.
Jamie Scotcherbiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.
Riccha Sethibiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.
Shirong Yubiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.
Nick Hardingbiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.
Mark Hillbiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.
Ermira Lleshibiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.
Casper Lumbybiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.ORCID http://orcid.org/0000-0001-8329-9228
Jean Teyssandierbiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.
Michael Wilsonbiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.
Robert Crawfordbiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.ORCID http://orcid.org/0009-0003-2487-4626
Tom Charlesworthbiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.
Páidí Creedbiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.
Shankar Balasubramanianbiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK.ORCID http://orcid.org/0000-0002-0281-5815
Robert J Osbornebiomodal Ltd, The Trinity Building, Chesterford Research Park, Cambridge, UK. robert.osborne@biomodal.com.ORCID http://orcid.org/0000-0002-1914-1239

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEarly cancer detection has the potential to significantly improve treatment outcomes and survival rates. This study investigates the roles of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) as biomarkers for early-stage colorectal cancer (CRC) detection in cell-free DNA (cfDNA).

methodsWe analyzed cfDNA from 37 treatment-naive CRC patients and 32 healthy controls using duet evoC 6-base whole genome sequencing (A, C, T, G, 5mC, 5hmC). We then built CRC classifiers using differentially methylated regions identified in stage IV CRC tissue samples. We compared the performance of models using 5mC-only, 5hmC-only, modified cytosine, or 5mC and 5hmC features.

resultsHere we show that models combining measurements of 5mC and 5hmC significantly enhance diagnostic accuracy (AUC = 0.95) compared to traditional approaches that conflate these markers (modified C, AUC = 0.66). Notably, of all the DMRs considered, almost half show an increase in 5hmC at stage I and a corresponding decrease in 5mC at stage IV, suggesting that 5hmC can effectively track regions undergoing demethylation during tumor development.

conclusionsThese results support the hypothesis that distinguishing between 5mC and 5hmC improves the sensitivity of liquid biopsy tests for early-stage cancer detection.

Identifiers

PMID41559405
PMCPMC12819408

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.