Evidence mapPaperPMID 42337646Full record

ArticleJournal of translational medicine2026

Exploring epigenome-proteome interactions underlying post-surgical progression of non-functioning pituitary adenomas using hypernetwork modelling.

Medha Suman, Tobias Hallén, Terence Garner, Annika Thorsell, Adam Stevens, Linus Köster, Helena Carén, Oskar Ragnarsson, Thomas Skoglund, Gudmundur Johannsson

Abstract read
In one paragraph

Article in Journal of translational medicine, 2026. 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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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

10 authors.

Medha SumanDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SU Sahlgrenska, Göteborg, 41345, Sweden. medha.suman@gu.se.ORCID http://orcid.org/0000-0001-8432-7227
Tobias HallénDepartment of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-3628-7686
Terence GarnerDivision of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0003-3962-9730
Annika ThorsellProteomics Core Facility, BioMS, SciLifeLab, University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-3392-7764
Adam StevensDivision of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-1950-7325
Linus KösterDepartment of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden.ORCID http://orcid.org/0009-0000-7547-0339
Helena CarénSahlgrenska Center for Cancer Research, Department of Medical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-8584-555X
Oskar RagnarssonDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SU Sahlgrenska, Göteborg, 41345, Sweden.ORCID http://orcid.org/0000-0003-0204-9492
Thomas SkoglundDepartment of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden.ORCID http://orcid.org/0000-0003-2645-3529
Gudmundur JohannssonDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SU Sahlgrenska, Göteborg, 41345, Sweden.ORCID http://orcid.org/0000-0003-3484-8440

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNon-functioning pituitary adenomas (NFPAs) present a complex clinical challenge due to their indolent and invasive growth patterns, and critical anatomical location. Post-surgical tumor progression is frequent in patients with NFPAs, which often necessitates additional therapeutic interventions. The molecular mechanisms underlying post-surgical progression remain poorly understood and there are currently no reliable methods to stratify patients according to risk of tumor progression. The aim of this study was to comprehensively characterize the molecular alterations, together with an integrated understanding of their interactions, that could potentially uncover the biological processes driving post-surgical tumor progression of NFPAs.

methodsWe performed an integrated analysis of genome-wide DNA methylation and proteomics in 25 progressive and 15 indolent NFPAs using hypernetwork modelling linking CpG sites to the differentially expressed proteins to identify functional alterations associated with tumor progression. In addition, we investigated cis-regulatory relationships by examining CpG sites located within or in close proximity to the genes encoding the corresponding proteins, allowing assessment of the direct impact of DNA methylation changes on protein expression levels.

resultsHypernetwork analysis uncovered extensive indirect and higher-order associations, capturing coordinated epigenetic influences on protein networks in indolent and progressive NFPAs. Progressive NFPAs were characterized by a compact and highly interconnected hub network with proteins primarily involved in DNA replication and transcription regulation (MCM6 and HDGFL2), chromatin organization (SAFB, HDGFL2, KDM3B, and TAF7), and cytoskeleton organization and cell structure maintenance (AJM1 and SYNE2). In contrast, indolent adenomas exhibited a broader and more diffuse network architecture with hub proteins linked to protein processing and transport (PSMD6, APMAP, B4GAT1, and COPE), extracellular matrix organization (LAMB2), and oxidative stress response (CISD2). Hub proteins in progressive NFPAs were enriched for metabolic pathways including glycolysis and tricarboxylic acid cycle, while enriched pathways for hub proteins in the indolent group were associated with genome maintenance and cellular stress responses.

conclusionsHypernetwork analysis highlighted distinct epigenetic-proteomic regulatory mechanisms linked to tumor behavior that were not detected through cis-acting correlation analysis. Collectively, this integrative approach provides insight beyond direct regulation effects and offers a framework for identifying network-informed candidate markers with mechanistic relevance in tumor progression.

Indexed as

AdenomaDisease ProgressionEpigenomeModels, BiologicalPituitary NeoplasmsProteomeCpG IslandsDNA MethylationEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansMaleProteomicsProteomeDNA methylationHypernetworkNon-functioning pituitary adenomaProtein expressionTumor progression

Identifiers

PMID42337646
PMCPMC13295522

What Socratic holds

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LicenceCC BY
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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.