ArticleNeuro-oncology2023
Integrated longitudinal analysis of adult grade 4 diffuse gliomas with long-term relapse interval revealed upregulation of TGF-β signaling in recurrent tumors.
Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
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- Identification and validation of exosome-related biomarkers in pediatric glioblastoma.Discover oncology · 2026Article
- Comparing Utility of Intraoperative Magnetic Resonance Imaging and 5-Aminolevulinic Acid in High-Grade Glioma Resection Surgery: A Systematic Review and Meta-Analysis.Neurosurgery practice · 2025Review
- Non-canonical ALK7 pathways promote pancreatic cancer metastasis through β-catenin/MMP-mediated basement membrane breakdown and intravasation.Molecular cancer · 2025Article
- Esophageal squamous cell carcinoma susceptibility of activin A receptor type 1C variants in Chinese population.World journal of gastrointestinal oncology · 2025Article
- ADAR1-regulated miR-142-3p/RIG-I axis suppresses antitumor immunity in nasopharyngeal carcinoma.Non-coding RNA research · 2025Article
- Single-cell RNA sequencing identifies a subtype of FN1 + tumor-associated macrophages associated with glioma recurrence and as a biomarker for immunotherapy.Biomarker research · 2024Article
- Unveiling divergent treatment prognoses in IDHwt-GBM subtypes through multiomics clustering: a swift dual MRI-mRNA model for precise subtype prediction.Journal of translational medicine · 2024Article
- Adjuvant convection-enhanced delivery for the treatment of brain tumors.Journal of neuro-oncology · 2024Review
- Targeting drug-tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells.MedComm · 2023Review
- Review
- NMI: a potential biomarker for tumor prognosis and immunotherapy.Frontiers in pharmacology · 2022Article
- Proteins of the cancer cell secretome induce the protumoral microenvironment of diffuse intrinsic pontine glioma.Neuro-oncology advancesArticle
- miR-644a is a tumor cell-intrinsic mediator of sex bias in glioblastoma.Neuro-oncology advancesArticle
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAdult-type diffuse gliomas, CNS WHO grade 4 are the most aggressive primary brain tumors and represent a particular challenge for therapeutic intervention.
methodsIn a single-center retrospective study of matched pairs of initial and post-therapeutic glioma cases with a recurrence period greater than 1 year, we performed whole exome sequencing combined with mRNA and microRNA expression profiling to identify processes that are altered in recurrent gliomas.
resultsMutational analysis of recurrent gliomas revealed early branching evolution in 75% of the patients. High plasticity was confirmed at the mRNA and miRNA levels. SBS1 signature was reduced and SBS11 was elevated, demonstrating the effect of alkylating agent therapy on the mutational landscape. There was no evidence for secondary genomic alterations driving therapy resistance. ALK7/ACVR1C and LTBP1 were upregulated, whereas LEFTY2 was downregulated, pointing towards enhanced Tumor Growth Factor β (TGF-β) signaling in recurrent gliomas. Consistently, altered microRNA expression profiles pointed towards enhanced Nuclear Factor Kappa B and Wnt signaling that, cooperatively with TGF-β, induces epithelial to mesenchymal transition (EMT), migration, and stemness. TGF-β-induced expression of pro-apoptotic proteins and repression of antiapoptotic proteins were uncoupled in the recurrent tumor.
conclusionsOur results suggest an important role of TGF-β signaling in recurrent gliomas. This may have clinical implications since TGF-β inhibitors have entered clinical phase studies and may potentially be used in combination therapy to interfere with chemoradiation resistance. Recurrent gliomas show high incidence of early branching evolution. High tumor plasticity is confirmed at the level of microRNA and mRNA expression profiles.
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