Evidence map›Paper›PMID 41261178›Full record

ArticleCommunications biology2025

5-hydroxymethylcytosine analysis reveals stable epigenomic changes in tumor tissue that enable cancer detection in cell-free DNA.

Yuan Xue, Yuhong Ning, Verena Friedl, David Haan, Anna Bergamaschi, Gulfem D Guler, Kyle Hazen, Aaron Scott, Tierney Phillips, Erin McCarthy and 11 more

Abstract read
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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  5. Review
  6. 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

21 authors.

Yuan Xue *ClearNote Health, San Mateo, CA, USA.
Yuhong Ning *ClearNote Health, San Mateo, CA, USA.
Verena FriedlClearNote Health, San Mateo, CA, USA.
David HaanClearNote Health, San Diego, CA, USA.
Anna BergamaschiClearNote Health, San Diego, CA, USA.
Gulfem D GulerClearNote Health, San Mateo, CA, USA.
Kyle HazenClearNote Health, San Mateo, CA, USA.
Aaron ScottClearNote Health, San Mateo, CA, USA.
Tierney PhillipsClearNote Health, San Diego, CA, USA.
Erin McCarthyClearNote Health, San Diego, CA, USA.
Christopher K EllisonClearNote Health, San Diego, CA, USA.
Roger MaltaClearNote Health, San Diego, CA, USA.
Albert NguyenClearNote Health, San Diego, CA, USA.
Vanessa LopezClearNote Health, San Diego, CA, USA.
Romola CavetClearNote Health, San Diego, CA, USA.
Melissa PetersClearNote Health, San Diego, CA, USA.
Judith SheardClearNote Health, San Diego, CA, USA.
William GibbClearNote Health, San Mateo, CA, USA.
Shimul ChowdhuryClearNote Health, San Diego, CA, USA.
Wayne VolkmuthClearNote Health, San Mateo, CA, USA.
Samuel LevyClearNote Health, San Diego, CA, USA. slevy@clearnotehealth.com.ORCID http://orcid.org/0000-0002-4444-5103

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

5-hydroxymethylcytosine (5hmC) is a stable epigenomic mark associated with gene regulation and tumorigenesis. To evaluate its potential for multi-cancer detection, epigenomic distribution of 5hmC was analyzed in tumor tissues (n = 217), normal tissues (n = 50), and cell-free DNA (cfDNA) from cancer (n = 1009) and non-cancer subjects (n = 1678) across breast, colon, lung, ovarian, and pancreatic cancers. Differential analysis revealed extensive redistribution of 5hmC in early-stage tumors that persisted into the late-stage, while global 5hmC abundance decreased in all tumors. Two distinct patterns of hydroxymethylation distribution were identified: one common across cancers and another tissue specific. Differential hydroxymethylation regions (DhmRs) that were tumor tissue specific had significantly improved cancer prediction in cfDNA. A multinomial logistic regression model was trained on tissue-specific DhmRs to predict Tissue of Tumor Origin (TOTO) of cfDNA with 85.2% accuracy. These findings demonstrate that stable, cancer-specific 5hmC signatures appear to be established early in tumorigenesis persist throughout disease progression, suggesting 5hmC as a potential pan-cancer marker for early and late-stage tumor detection via liquid biopsy.

Indexed as

5-MethylcytosineCell-Free Nucleic AcidsEpigenesis, GeneticNeoplasmsBiomarkers, TumorDNA MethylationEpigenomicsFemaleHumans5-hydroxymethylcytosine5-MethylcytosineBiomarkers, TumorCell-Free Nucleic Acids

Identifiers

PMID41261178
PMCPMC12630682

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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.