Evidence map›Paper›PMID 42169093›Full record

ArticleBiology of sex differences2026

Gene regulatory network analysis identifies dysregulation of hypoxia pathways as contributing to glioblastoma treatment resistance in females.

Tomisin Adebari, Viola Fanfani, Marouen Ben Guebila, Derrick DeConti, Katherine Hoff Shutta, Camila M Lopes-Ramos, Lauren Hsu, Dawn L DeMeo, John Quackenbush, Tara Eicher

Abstract read
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In one paragraph

Article in Biology of sex differences, 2026. 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

5 · Who and what money

Authors and funding

10 authors.

Tomisin AdebariDepartment of Biomedical Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD, 21218, USA.
Viola FanfaniDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Ave, Boston, MA, 02115, USA.
Marouen Ben GuebilaDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Ave, Boston, MA, 02115, USA.
Derrick DeContiDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Ave, Boston, MA, 02115, USA.
Katherine Hoff ShuttaDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Ave, Boston, MA, 02115, USA.
Camila M Lopes-RamosDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Ave, Boston, MA, 02115, USA.
Lauren HsuDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Ave, Boston, MA, 02115, USA.
Dawn L DeMeoChanning Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Ave, Boston, MA, 02115, USA.
John QuackenbushDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Ave, Boston, MA, 02115, USA.
Tara EicherDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Ave, Boston, MA, 02115, USA. teicher@hsph.harvard.edu.

Funding

Unraveling the Complexities of Risk and Mechanism in CancerR35CA220523 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI QUACKENBUSH, JOHN · 2018 to 2024
$6.0M
WebMeV: A Robust Platform for Intuitive Genomic Data AnalysisU24CA231846 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI QUACKENBUSH, JOHN · 2019 to 2023
$3.2M
Interdisciplinary training: Statistical Genetics/Genomics and Computational BiologyT32GM135117 · NIGMS · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Curtis Huttenhower, XIHONG LIN · 2020 to 2026
$3.1M
Networks Tools to Understand Sex- and Gender-Specific Drivers of DiseaseR01HG011393 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI DEMEO, DAWN L, QUACKENBUSH, JOHN · 2021 to 2024
$2.1M
Mentoring in Patient Oriented Research in Lung Disease through the Lens of Sex as a Biological VariableK24HL171900 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI DAWN L DEMEO · 2024 to 2026
$386k
Resolving phenotypic overlap in renal carcinoma subtypes using multi-tiered network methodsK25CA297149 · NCI · DANA-FARBER CANCER INST · PI Marouen Ben Guebila · 2025 to 2026
$340k
Sex chromosome gene regulatory networks and COPDK01HL166376 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOPES-RAMOS, CAMILA · 2023 to 2024
$324k
Multi-omic network methods for mapping molecular trajectories of age-related lung diseasesK25HL175222 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI Katherine Hoff Shutta · 2025 to 2026
$267k
NCI NIH HHS K25 CA297149NCI NIH HHS K25CA297149NCI NIH HHS R35 CA220523NCI NIH HHS R35CA220523NCI NIH HHS U24 CA231846NCI NIH HHS U24CA231846NHGRI NIH HHS R01 HG011393NHGRI NIH HHS R01HG011393NHLBI NIH HHS K01 HL166376NHLBI NIH HHS K01HL166376NHLBI NIH HHS K24 HL171900NHLBI NIH HHS K24HL171900NHLBI NIH HHS K25 HL175222NHLBI NIH HHS K25HL175222NIGMS NIH HHS T32 GM135117NIGMS NIH HHS T32GM135117
6 · The paper itself

Abstract

backgroundGlioblastoma or GBM (IDH wild-type) is an aggressive brain tumor that is notoriously resistant to treatment, with an average survival time of 17 months. While the overall outcome is poor for both males and females, sex differences in GBM incidence and outcome suggest sex-specific biological mechanisms underlie tumorigenesis. In contrast, low-grade glioma (LGG) is a less aggressive brain tumor that tends to have a better prognosis and a longer survival time.

methodsTo understand mechanisms contributing to treatment resistance in GBM in both males and females, we inferred gene regulatory networks (GRNs) for males and females with LGG and GBM using RNA-seq data from The Cancer Genome Atlas (TCGA). We analyzed these to identify both sex-specific and sex-stratified gene regulation in GBM. We then validated these results on a separate cohort, the Repository of Molecular BRAin Neoplasia DaTa (REMBRANDT).

resultsWe found sex-specific differential targeting of several pathways, including hypoxia and related pathways (carbohydrate metabolism, innate immune processes, and extracellular matrix pathways) known to be dysregulated in hypoxic conditions, in GBM when compared against LGG. After further evaluating the co-regulation of sex-specific pathways in GBM, we found that females exhibited a greater degree of co-regulation between hypoxia and hypoxia-associated transcriptional programs with the aforementioned downstream pathways than did males.

conclusionsOur results suggest that dysregulation of hypoxia-related pathways in GBM plays a female-specific role in resistance to treatment and overall outcomes.

Indexed as

Brain NeoplasmsDrug Resistance, NeoplasmGene Regulatory NetworksGlioblastomaSex CharacteristicsFemaleGene Expression Regulation, NeoplasticHumansMaleGene expressionGene regulatory networkGlioblastomaHypoxiaLow-grade gliomaTranscription factorTreatment resistance

Identifiers

PMID42169093
PMCPMC13371200

What Socratic holds

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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.