Evidence map›Paper›PMID 41353171›Full record

ArticleHuman genomics2025

Genome-wide methylation profiles of primary and matched distant metastasis: insights from the Dutch Early-Stage melanoma (D-ESMEL) study.

Jasper Ouwerkerk, Thamila Kerkour, Antien Mooyaart, Catherine Zhou, Ruben Boers, Joachim Boers, Joost Gribnau, Marlies Wakkee, Yunlei Li, Loes Hollestein

Abstract read
In one paragraph

Article in Human genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Jasper Ouwerkerk *Department of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Rotterdam, 3015 CN, The Netherlands.ORCID 0000-0003-2556-2125
Thamila Kerkour *Department of Dermatology, Erasmus Medical Center, Rotterdam, 3015 CN, The Netherlands.ORCID 0000-0002-5857-1792
Antien MooyaartDepartment of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Rotterdam, 3015 CN, The Netherlands.ORCID 0000-0001-9810-5780
Catherine ZhouDepartment of Dermatology, Erasmus Medical Center, Rotterdam, 3015 CN, The Netherlands.ORCID 0009-0002-7157-6341
Ruben BoersDepartment of Developmental Biology, Erasmus Medical Center, Rotterdam, 3015 CN, The Netherlands.ORCID 0000-0002-3377-2897
Joachim BoersDepartment of Developmental Biology, Erasmus Medical Center, Rotterdam, 3015 CN, The Netherlands.
Joost GribnauDepartment of Developmental Biology, Erasmus Medical Center, Rotterdam, 3015 CN, The Netherlands.
Marlies WakkeeDepartment of Dermatology, Erasmus Medical Center, Rotterdam, 3015 CN, The Netherlands.ORCID 0000-0001-8578-901X
Yunlei LiDepartment of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Rotterdam, 3015 CN, The Netherlands.ORCID 0000-0002-5697-1602
Loes HollesteinDepartment of Dermatology, Erasmus Medical Center, Rotterdam, 3015 CN, The Netherlands. l.hollestein@erasmusmc.nl.ORCID 0000-0001-8922-6791

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEarly-stage (stage I-II) cutaneous melanoma accounts for the majority of melanoma diagnoses. However, more than 40% of patients who die due to melanoma were initially diagnosed with an early-stage melanoma. This highlights the current limitations of the Tumor Node Metastasis (TNM) staging and shows that additional biomarkers, prognostic for distant metastasis, need to be identified.

methodsThe aim of this study was to identify prognostic genome-wide methylation markers of metastasized primary early-stage melanomas and retrieving biological insights from its matched distant metastasis. We selected 45 samples from the Dutch Early-Stage Melanoma (D-ESMEL) study, representing case-control sets where the primary melanoma of each metastatic case (n = 15) is matched to a primary melanoma of a control (n = 15) based on known clinical risk factors. Matched distant metastasis (n = 15) were also retrieved. Laser capture microdissection was performed to isolate the tumor tissue, where after a genome-wide methylated DNA sequencing (MeD-seq) was conducted. After quality control, a total of 30 samples were retained for analysis, including 11 controls, 9 cases, and 10 metastatic samples. Differentially methylated regions (DMR) between primary tumors of the cases-control sets and the tumor of the primary case and its metastasis were tested using Chi-squared test with a genome-wide sliding window analysis, as well as a paired t-test in predefined promotor, gene body, and CpG-island regions.

resultsMeD-seq analyses did not reveal prognostic methylation markers in primary melanomas, which have additional prognostic value on top of known clinical risk factors after correction for multiple testing. However, exploratory analysis before correction revealed eight protein coding genes with the largest methylation difference between primary melanomas of patients with and without metastasis and between primary melanomas and matched distant metastasis: CYP2E1, PTPRN2, CHCHD2, NDRG2, EDN2, GC, USP17L1, and SERPINB8.

conclusionThis study found 8 genes that have been implicated in primary tumors or metastasis of other cancers which require further investigation into their involvement of metastasis in melanoma.

Indexed as

Biomarkers, TumorDNA MethylationMelanomaSkin NeoplasmsAdultAgedCase-Control StudiesCutaneous Malignant MelanomaFemaleGene Expression Regulation, NeoplasticGenome-Wide Association StudyHumansMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingBiomarkers, TumorD-ESMELGenome-wideMelanomaMetastasisMethylation

Identifiers

PMID41353171
PMCPMC12797433

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.