ArticleAnnals of clinical and translational neurology2019
Integrated systems-genetic analyses reveal a network target for delaying glioma progression.
Article in Annals of clinical and translational neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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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.
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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.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Identification of gene regulatory networks affected across drug-resistant epilepsies.Nature communications · 2024Article
- Involvement of Resveratrol against Brain Cancer: A Combination Strategy with a Pharmaceutical Approach.Molecules (Basel, Switzerland) · 2022Review
- Systematic analysis to identify transcriptome-wide dysregulation of Alzheimer's disease in genes and isoforms.Human genetics · 2021Article
- Differential Co-Expression Analyses Allow the Identification of Critical Signalling Pathways Altered during Tumour Transformation and Progression.International journal of molecular sciences · 2020Review
- The Plant-Derived Compound Resveratrol in Brain Cancer: A Review.Biomolecules · 2020Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
objectiveTo identify a convergent, multitarget proliferation characteristic for astrocytoma transformation that could be targeted for therapy discovery.
methodsUsing an integrated functional genomics approach, we prioritized networks associated with astrocytoma progression using the following criteria: differential co-expression between grade II and grade III IDH1-mutated and 1p/19q euploid astrocytomas, preferential enrichment for genetic risk to cancer, association with patient survival and sample-level genomic features. Drugs targeting the identified multitarget network characteristic for astrocytoma transformation were computationally predicted using drug transcriptional perturbation data and validated using primary human astrocytoma cells.
resultsA single network, M2, consisting of 177 genes, was associated with glioma progression on the basis of the above criteria. Functionally, M2 encoded physically interacting proteins regulating cell cycle processes and analysis of genome-wide gene-regulatory interactions using mutual information and DNA-protein interactions revealed the known regulators of cell cycle processes FoxM1, B-Myb, and E2F2 as key regulators of M2. These results suggest functional disruption of M2 via gene mutation or altered expression as a convergent pathway regulating astrocytoma transformation. By considering M2 as a multitarget drug target regulating astrocytoma transformation, we identified several drugs that are predicted to restore M2 expression in anaplastic astrocytoma toward its low-grade profile and of these, we validated the known antiproliferative drug resveratrol as down-regulating multiple nodes of M2 including at nanomolar concentrations achievable in human cerebrospinal fluid by oral dosing.
interpretationOur results identify M2 as a multitarget network characteristic for astrocytoma progression and encourage M2-based drug screening to identify new compounds for preventing glioma transformation.
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Registered trials
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.