Evidence map›Paper›PMID 41969430›Full record

ArticleNeuro-oncology advances

DNA methylation-based deconvolution study of glioblastoma heterogeneity and identification of cell compositions associated with patient survival.

Aviel Iluz, Nir Lavi, Hanna Charbit, Mijal Gutreiman, Masha Idelson, Debora Steiner, Etti Ben-Shushan, Aviad Zick, Amir Eden, Anat Mordechai and 6 more

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Article in Neuro-oncology advances. 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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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

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5 · Who and what money

Authors and funding

16 authors.

Aviel IluzLeslie and Michael Gaffin Center for Neuro-Oncology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.ORCID https://orcid.org/0009-0007-6730-3056
Nir LaviLeslie and Michael Gaffin Center for Neuro-Oncology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Hanna CharbitLeslie and Michael Gaffin Center for Neuro-Oncology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Mijal GutreimanLeslie and Michael Gaffin Center for Neuro-Oncology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Masha IdelsonHadassah Human Stem Cells Research Center, Goldyne Savad Institute of Gene Therapy, Department of Obstetrics and Gynecology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Debora SteinerHadassah Human Stem Cells Research Center, Goldyne Savad Institute of Gene Therapy, Department of Obstetrics and Gynecology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Etti Ben-ShushanHadassah Human Stem Cells Research Center, Goldyne Savad Institute of Gene Therapy, Department of Obstetrics and Gynecology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Aviad ZickOncology Department, Sharett Institute of Oncology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.ORCID https://orcid.org/0000-0002-5077-9249
Amir EdenDepartment of Genetics, The Hebrew University of Jerusalem, Jerusalem, Israel.
Anat MordechaiLeslie and Michael Gaffin Center for Neuro-Oncology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Moscovici SamuelDepartment of Pathology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Yakov FelligDepartment of Pathology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Alexander LossosLeslie and Michael Gaffin Center for Neuro-Oncology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Joshua MossOncology Department, Sharett Institute of Oncology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Benjamin E ReubinoffHadassah Human Stem Cells Research Center, Goldyne Savad Institute of Gene Therapy, Department of Obstetrics and Gynecology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Iris LavonLeslie and Michael Gaffin Center for Neuro-Oncology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.ORCID https://orcid.org/0000-0002-6526-1573

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) is an aggressive, heterogeneous brain tumor with limited treatment options. This study employs DNA methylation-based deconvolution of GBM to define its cellular composition and its association with patient outcomes. Methods: We generated oligodendroglial precursor cells at various developmental stages from enriched human neural progenitor cultures and used their DNA methylation signatures, along with published signatures of brain tumor cell types and the tumor microenvironment, to deconvolve 263 adult GBMs (Heidelberg cohort). An independent cohort of 199 GBMs from The Cancer Genome Atlas (TCGA) and GEO, all treated with standard-of-care therapy, was similarly deconvolved. Kaplan-Meier survival analysis was used to assess the prognostic value of the neoplastic components. Results: GBM deconvolution uncovered distinct cellular compositions that differed between the neoplastic and non-neoplastic component. The neoplastic fractions averaged 70% of the tumor bulk and were predominantly composed of oligodendrocyte-like (43%) cell populations, in addition to oligodendrocyte precursor-like (27%), astrocyte-like (19%), and mesenchymal stem cell-like (11%) populations. The non-neoplastic fractions were enriched for macrophages, vascular cells, and immune cell populations. A higher oligodendrocyte-like signature was linked to poorer survival (median survival 14.3 vs. 15.3 months; Conclusions: The methylation-based deconvolution data and analyses provided insight into GBM heterogeneity and highlighted the prognostic potential of the astrocyte-to-oligodendrocyte ratio and its application in personalized treatment strategies.

Indexed as

central nervous system tumordeconvolution­glioblastomamethylation signaturetumor heterogeneity

Identifiers

PMID41969430
PMCPMC13064926

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