Evidence map›Paper›PMID 41286274›Full record

ArticleScientific reports2025

DNA methyltransferase 1 correlates with immune modulation in pancreatic neuroendocrine tumors.

Zena Saleh, Rachel J Nation, Matthew C Moccia, Ami Kalola, Yazid Ghanem, Hansa Joshi, Upasana Joneja, Yahui Li, Francis Spitz, Tao Gao and 1 more

Abstract read
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In one paragraph

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

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

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

11 authors.

Zena SalehSurgical Research Lab, Department of Surgery, Cooper University Health Care, Cooper Medical School of Rowan University, 401 Haddon Ave, Camden, NJ, 08103, USA.
Rachel J NationSurgical Research Lab, Department of Surgery, Cooper University Health Care, Cooper Medical School of Rowan University, 401 Haddon Ave, Camden, NJ, 08103, USA.
Matthew C MocciaSurgical Research Lab, Department of Surgery, Cooper University Health Care, Cooper Medical School of Rowan University, 401 Haddon Ave, Camden, NJ, 08103, USA.
Ami KalolaSurgical Research Lab, Department of Surgery, Cooper University Health Care, Cooper Medical School of Rowan University, 401 Haddon Ave, Camden, NJ, 08103, USA.
Yazid GhanemSurgical Research Lab, Department of Surgery, Cooper University Health Care, Cooper Medical School of Rowan University, 401 Haddon Ave, Camden, NJ, 08103, USA.
Hansa JoshiSurgical Research Lab, Department of Surgery, Cooper University Health Care, Cooper Medical School of Rowan University, 401 Haddon Ave, Camden, NJ, 08103, USA.
Upasana JonejaDepartment of Pathology, Cooper University Health Care, Camden, NJ, 08103, USA.
Yahui LiSurgical Research Lab, Department of Surgery, Cooper University Health Care, Cooper Medical School of Rowan University, 401 Haddon Ave, Camden, NJ, 08103, USA.
Francis SpitzSurgical Research Lab, Department of Surgery, Cooper University Health Care, Cooper Medical School of Rowan University, 401 Haddon Ave, Camden, NJ, 08103, USA.
Tao GaoSurgical Research Lab, Department of Surgery, Cooper University Health Care, Cooper Medical School of Rowan University, 401 Haddon Ave, Camden, NJ, 08103, USA. gao-tao@cooperhealth.edu.
Young Ki HongSurgical Research Lab, Department of Surgery, Cooper University Health Care, Cooper Medical School of Rowan University, 401 Haddon Ave, Camden, NJ, 08103, USA. hong-young@cooperhealth.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epigenetic regulation is a key driver of pancreatic neuroendocrine tumors (PNETs), yet the interplay between epigenetics and immune infiltration in the PNET tumor microenvironment remains poorly understood. This study investigates associations between epigenetic regulators and immune markers in PNETs to evaluate the potential for a combination of epigenetic-targeted therapy and immunotherapy. Immunohistochemical staining was performed on specimens from twenty-five Grade 1 or Grade 2 PNET patients, along with matched adjacent benign controls from each individual. Quantification was conducted using ImageJ software, followed by statistical analysis to assess correlations between epigenetic regulation and immune modulation. DNA methyltransferase 1 (DNMT1) was significantly upregulated in PNET samples, positively correlated with higher tumor grades and negatively correlated with 5-hydroxymethylcytosine (5-HMC) levels. Overexpression of DNMT3A and DNMT3B was also observed. Additionally, immune markers such as CD3, CD8, CCL5, and NFκB were significantly elevated, with CCL5 showing a grade-dependent increase. Interestingly, while PD-L2 was upregulated in tumors, there were no differences in the expression levels of PD-L1 and FOXP3 between PNET and adjacent benign controls. Additionally, DNMT1 expression positively correlated with Ki67, CD3, PD-L2, and CCL5 while inversely correlating with Menin. These findings suggest DNMT1 plays a significant role in immune modulation during PNET progression, highlighting the potential of combining DNMT1 inhibitors with immune checkpoint blockade as a therapeutic strategy to enhance outcomes for PNET patients.

Indexed as

DNA (Cytosine-5-)-Methyltransferase 1Neuroendocrine TumorsPancreatic Neoplasms5-MethylcytosineAdultAgedBiomarkers, TumorDNA (Cytosine-5-)-MethyltransferasesEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedTumor Microenvironment5-MethylcytosineBiomarkers, TumorDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNMT1 protein, humanDNA methyltransferase 1Epigenetic regulationImmune modulationPancreatic neuroendocrine tumorTumor gradeTumor progression

Identifiers

PMID41286274
PMCPMC12644564

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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.