Evidence map›Paper›PMID 41006121›Full record

ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2025

LINE-1 hypomethylation in cell-free DNA of high-grade glioma patients correlates with tissue levels and is associated with reduced DNMT1 and H4K20me3 expression.

Angeliki-Ioanna Giannopoulou, Panagiotis Skouras, Panagiotis Sarantis, Alkinoos Armoundas, Kostas Palamaris, Antonios N Gargalionis, Athanasia Sepsa, Efstathios Boviatsis, Theodosis Kalamatianos, George Stranjalis and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2025. 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
–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

2 citing papers in PubMed.

  1. Review
  2. 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.

Angeliki-Ioanna GiannopoulouDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg. 16, 11527 Athens, Greece.
Panagiotis SkourasDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg. 16, 11527 Athens, Greece; 1st Department of Neurosurgery, Evangelismos Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece.
Panagiotis SarantisDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg. 16, 11527 Athens, Greece.
Alkinoos ArmoundasDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg. 16, 11527 Athens, Greece.
Kostas PalamarisDepartment of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Antonios N GargalionisDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg. 16, 11527 Athens, Greece.
Athanasia SepsaDepartment of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Efstathios BoviatsisSecond Department of Neurosurgery, "Attikon" University Hospital, National and Kapodistrian University of Athens, 15772 Athens, Greece.
Theodosis Kalamatianos1st Department of Neurosurgery, Evangelismos Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece; Department of Biomedical Engineering, University of West Attica, 122 43 Athens, Greece.
George Stranjalis1st Department of Neurosurgery, Evangelismos Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece.
Penelope KorkolopoulouDepartment of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Sarantis ChlamydasDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg. 16, 11527 Athens, Greece; Olink Proteomics, 75330, Uppsala, Sweden.
Athanasios G PapavassiliouDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg. 16, 11527 Athens, Greece. Electronic address: papavas@med.uoa.gr.
Christina PiperiDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg. 16, 11527 Athens, Greece. Electronic address: cpiperi@med.uoa.gr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gliomas exhibit diverse genetic, molecular, and histological profiles with limited liquid biopsy biomarkers. Loss of Long Interspersed Nuclear Element-1 (LINE-1) methylation confers to genomic instability and tumorigenesis, primarily mediated by DNA methyltransferase 1 (DNMT1) through interaction with histone H4 lysine 20 trimethylation (H4K20me3) and histone H3 lysine 9 trimethylation (H3K9me3). The present study evaluates the utility of liquid biopsy in detecting LINE-1 methylation in gliomas and potential correlations with DNMT1, H4K20me3, H3K9me3 tissue levels, clinicopathological characteristics and patients' survival. LINE-1 methylation was measured in cell-free DNA (cfDNA) of glioma patients' plasma prior to surgery or any adjuvant therapy and age-matched controls as well as in glioma tissues along with DNMT1, H4K20me3 and H3K9me3 expression. LINE-1 methylation content in plasma cfDNA and tissue samples was decreased significantly in grade 4 gliomas compared to controls (p ​< 0.0001, respectively). Similarly, DNMT1, H4K20me3 and H3K9me3 expression was significantly reduced in grade 4 cases compared to grade 2 (p ​< 0.0001). cfLINE-1 methylation was positively correlated with tissue LINE-1 methylation levels (p ​= 0.036) as well as with DNMT1 and H4K20me3 tissue expression in grade 4 samples (p ​< 0.0001, respectively). Moreover, low LINE-1 methylation plasma levels and tissue expression of DNMT1, H4K20me3 and H3K9me3 were correlated with worse overall survival in the entire cohort (p ​= 0.041, ​p ​= 0.016, ​p ​< 0.0001, ​p ​= 0.001, respectively). The present study supports the utility of liquid biopsy for the detection of LINE-1 hypomethylation, as a complementary prognostic biomarker for grade 4 tumors.

Indexed as

Brain NeoplasmsCell-Free Nucleic AcidsDNA (Cytosine-5-)-Methyltransferase 1DNA MethylationGliomaHistonesLong Interspersed Nucleotide ElementsAdultAgedBiomarkers, TumorFemaleHumansMaleMiddle AgedNeoplasm GradingBiomarkers, TumorCell-Free Nucleic AcidsDNA (Cytosine-5-)-Methyltransferase 1DNMT1 protein, humanHistonescfDNADNMT1GliomasH3K9me3H4K20me3LINE-1

Identifiers

PMID41006121
PMCPMC12664440

What OpenQuestion 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 OpenQuestion graph.