Evidence map›Paper›PMID 38635731›Full record

ArticlePloS one2024

Inhibition of cytosine 5-hydroxymethylation during progression of cancer precursor lesions in the uterine cervix.

Jobran M Moshi, Monique Ummelen, Frank Smedts, Frans C S Ramaekers, Anton H N Hopman

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 38% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Transcriptome sequencing (RNA-Seq) reveals non-coding pseudogene CDC27P9 role in cervical cancer.Apoptosis : an international journal on programmed cell death · 2026
    Article
  2. 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

5 authors at 2 institutions in 3 countries.

Jobran M MoshiDepartment of Molecular Cell Biology, GROW-School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands.
Monique UmmelenDepartment of Molecular Cell Biology, GROW-School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands.
Frank SmedtsDepartment of Pathology, Cork University Hospital, Cork, Ireland.
Frans C S RamaekersDepartment of Molecular Cell Biology, GROW-School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands.
Anton H N HopmanDepartment of Molecular Cell Biology, GROW-School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands.ORCID 0000-0002-5136-2955
Maastricht University · NLCork University Hospital · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Methylation and hydroxymethylation of cytosine moieties in CpG islands of specific genes are epigenetic processes shown to be involved in the development of cervical (pre)neoplastic lesions. We studied global (hydroxy)methylation during the subsequent steps in the carcinogenic process of the uterine cervix by using immunohistochemical protocols for the detection of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in paraffin-embedded tissues of the normal epithelia and (pre)malignant lesions. This approach allowed obtaining spatially resolved information of (epi)genetic alterations for individual cell populations in morphologically heterogeneous tissue samples. The normal ectocervical squamous epithelium showed a high degree of heterogeneity for both modifications, with a major positivity for 5-mC in the basal and parabasal layers in the ectocervical region, while 5-hmC immunostaining was even more restricted to the cells in the basal layer. Immature squamous metaplasia, characterized by expression of SOX17, surprisingly showed a decrease of 5-hmC in the basal compartments and an increase in the more superficial layers of the epithelium. The normal endocervical glandular epithelium showed a strong immunostaining reactivity for both modifications. At the squamocolumnar junctions, a specific 5-hmC pattern was observed in the squamous epithelium, resembling that of metaplasia, with the typical weak to negative reaction for 5-hmC in the basal cell compartment. The reserve cells underlying the glandular epithelium were also largely negative for 5-hmC but showed immunostaining for 5-mC. While the overall methylation status remained relatively constant, about 20% of the high-grade squamous lesions showed a very low immunostaining reactivity for 5-hmC. The (pre)malignant glandular lesions, including adenocarcinoma in situ (AIS) and adenocarcinoma showed a progressive decrease of hydroxymethylation with advancement of the lesion, resulting in cases with regions that were negative for 5-hmC immunostaining. These data indicate that inhibition of demethylation, which normally follows cytosine hydroxymethylation, is an important epigenetic switch in the development of cervical cancer.

Indexed as

Carcinoma, Squamous CellUterine Cervical Neoplasms5-MethylcytosineCervix UteriCytosineDNA MethylationFemaleHumansMetaplasia5-MethylcytosineCytosine

Identifiers

PMID38635731
PMCPMC11025792
OpenAlexW4394933457

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.