Evidence map›Paper›PMID 41369112›Full record

ArticleNeuro-oncology2026

DNA methylation profiling predicts postsurgical regrowth in SF1-lineage nonfunctioning pituitary neuroendocrine tumors.

Morten Winkler Møller, Grayson A Herrgott, Marianne Skovsager Andersen, Bo Halle, Christian Bonde Pedersen, Henning Bünsow Boldt, Jeanette K Petersen, Christopher Powell, Ana Valeria Castro, Frantz Rom Poulsen

Abstract read
In one paragraph

Article in Neuro-oncology, 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
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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

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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.

Morten Winkler MøllerDepartment of Neurosurgery, Odense University Hospital (M.W.M., B.H., C.B.P., F.R.P.).ORCID 0000-0001-5677-0969
Grayson A HerrgottHermelin Brain Tumor Center, Omics Laboratory, Department of Neurosurgery, Henry Ford Health (G.A.H., C.P., A.V.C.).
Marianne Skovsager AndersenDepartment of Endocrinology, Odense University Hospital (M.S.A.).ORCID 0000-0002-4603-9504
Bo HalleDepartment of Neurosurgery, Odense University Hospital (M.W.M., B.H., C.B.P., F.R.P.).
Christian Bonde PedersenDepartment of Neurosurgery, Odense University Hospital (M.W.M., B.H., C.B.P., F.R.P.).
Henning Bünsow BoldtDepartment of Clinical Research and BRIDGE (Brain Research-Inter Disciplinary Guided Excellence), University of Southern Denmark (M.W.M., B.H., C.B.P., H.B.B., J.K.P., F.R.P.).
Jeanette K PetersenDepartment of Clinical Research and BRIDGE (Brain Research-Inter Disciplinary Guided Excellence), University of Southern Denmark (M.W.M., B.H., C.B.P., H.B.B., J.K.P., F.R.P.).
Christopher PowellHermelin Brain Tumor Center, Omics Laboratory, Department of Neurosurgery, Henry Ford Health (G.A.H., C.P., A.V.C.).
Ana Valeria CastroHermelin Brain Tumor Center, Omics Laboratory, Department of Neurosurgery, Henry Ford Health (G.A.H., C.P., A.V.C.).
Frantz Rom PoulsenDepartment of Neurosurgery, Odense University Hospital (M.W.M., B.H., C.B.P., F.R.P.).

Funding

Beckett-Fonden, Aase og Ejnar Danielsens FondBrødrene Hartmanns FondNovo Nordisk FoundationOdense University HospitalTornøes og Høyrups Fond
6 · The paper itself

Abstract

backgroundNonfunctioning pituitary neuroendocrine tumors (NFPitNETs) account for ∼30-35% of PitNETs; ∼75% arise from the SF1 lineage. Recurrence remains common despite resection (∼30% in 10 years), and routine histopathology/IHC has limited value in predicting recurrence risk. This study evaluated whether DNA methylation profiling improves recurrence risk stratification. MATERIALS AND

methodsGenome-wide tissue methylation (Illumina EPIC v1, 850K) was analyzed in 117 retrospective NFPitNETs with clinical and imaging follow-up. Unsupervised consensus clustering defined methylation-based subgroups, followed by supervised differential methylation analysis to identify cluster-specific differentially methylated probes (DMPs). A classifier was trained using these signatures, with predicted subgroup memberships correlated with regrowth and progression-free survival (PFS). To ensure reliable estimations, longitudinal mixed-effects models were restricted to the interval of model stability (∼9 years), reflecting cohort follow-up. External validation was performed in 3 independent cohorts.

resultsFive clusters (k1-k5) emerged: 4 SF1-positive-predominant (k1, k2, k3, and k5) and 1 TPIT/PIT1-enriched NFPitNETs (k4). Among the 562 DMPs, many mapped to genes regulating cell-cycle and immune pathways. Compared with k1-k2, k3, k4, and k5 possessed significantly higher recurrence risk. Within SF1-lineage tumors, k3 exhibited postoperative tumor-volume expansion beginning at ∼6 years. The methylation-based classifier achieved ∼97% accuracy in assigning clusters and maintained prognostic separation across independent cohorts.

conclusionsDNA methylation profiling identifies biologically and clinically distinct NFPitNET subgroups, particularly within the SF1 lineage, and may enhance prediction of recurrence risk. Prospective validation and demonstration of clinical utility are warranted to support integration into precision management workflows.

Indexed as

Biomarkers, TumorDNA MethylationNeoplasm Recurrence, LocalNeuroendocrine TumorsPituitary NeoplasmsAdultAgedFemaleFollow-Up StudiesHumansMaleMiddle AgedPrognosisRetrospective StudiesSurvival RateBiomarkers, TumorDNA methylationmachine learningnonfunctioning ­PitNETsregrowthSF1

Identifiers

PMID41369112
PMCPMC13070495

What Socratic holds

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LicenceCC BY-NC
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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 Socratic graph.