ArticleThe American journal of pathology2012
The tumor microenvironment strongly impacts master transcriptional regulators and gene expression class of glioblastoma.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 1 of them a synthesis that pooled it.
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Who cites it
158 citing papers in PubMed, 1 synthesis or guideline pooled it, 227 citations in OpenAlex.
- The role of neuropathology in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline.Journal of neuro-oncology · 2014Guideline
- The role of NLRP3 inflammasome in 5-fluorouracil resistance of oral squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2017Trial
- Methyl 4-O-Demethylbarbatate Destabilises HIF-1α and Enhances Temozolomide Sensitivity in Glioma Cells.Cell proliferation · 2026Article
- Machine Learning-Based Classification of Gliomas and Tumor Grades with SHAP-Guided Feature Interpretation.Genes · 2026Article
- Melan-Dx: a knowledge-enhanced vision-language framework improves differential diagnosis of melanocytic neoplasm pathology.NPJ digital medicine · 2026Article
- HOXB5 in precision oncology: regulatory networks, functional duality, and clinical prospects.Journal of translational medicine · 2026Review
- Learning the cellular origins across cancers using single-cell chromatin landscapes.Nature communications · 2025Article
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- Multimodal fusion of radio-pathology and proteogenomics identify integrated glioma subtypes with prognostic and therapeutic opportunities.Nature communications · 2025Article
- Identification of C/EBPδ-Modifying Compounds as Potential Anticancer Agents Using a High-Throughput Drug Screen.Journal of cellular and molecular medicine · 2025Article
- C/EBPβ Regulates HIF-1α-Driven Invasion of Non-Small-Cell Lung Cancer Cells.Biomolecules · 2024Article
- ZBTB18 regulates cytokine expression and affects microglia/macrophage recruitment and commitment in glioblastoma.Communications biology · 2024Article
- Hypoxia Abrogates Tumor-Suppressive Activities of C/EBPδ in Pancreatic Cancer.International journal of molecular sciences · 2024Article
- Divergent transcriptomic signatures from putative mesenchymal stimuli in glioblastoma cells.Cancer gene therapy · 2024Article
- Review
- Comprehensive understanding of glioblastoma molecular phenotypes: classification, characteristics, and transition.Cancer biology & medicine · 2024Review
- Proneural-mesenchymal antagonism dominates the patterns of phenotypic heterogeneity in glioblastoma.iScience · 2024Article
- Neutrophils in glioma microenvironment: from immune function to immunotherapy.Frontiers in immunology · 2024Review
- Classification of bladder cancer based on immune cell infiltration and construction of a risk prediction model for prognosis.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Article
- Article
98 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The Cancer Genome Atlas (TCGA) project has generated gene expression data that divides glioblastoma (GBM) into four transcriptional classes: proneural, neural, classical, and mesenchymal. Because transcriptional class is only partially explained by underlying genomic alterations, we hypothesize that the tumor microenvironment may also have an impact. In this study, we focused on necrosis and angiogenesis because their presence is both prognostically and biologically significant. These features were quantified in digitized histological images of TCGA GBM frozen section slides that were immediately adjacent to samples used for molecular analysis. Correlating these features with transcriptional data, we found that the mesenchymal transcriptional class was significantly enriched with GBM samples that contained a high degree of necrosis. Furthermore, among 2422 genes that correlated with the degree of necrosis in GBMs, transcription factors known to drive the mesenchymal expression class were most closely related, including C/EBP-β, C/EBP-δ, STAT3, FOSL2, bHLHE40, and RUNX1. Non-mesenchymal GBMs in the TCGA data set were found to become more transcriptionally similar to the mesenchymal class with increasing levels of necrosis. In addition, high expression levels of the master mesenchymal factors C/EBP-β, C/EBP-δ, and STAT3 were associated with a poor prognosis. Strong, specific expression of C/EBP-β and C/EBP-δ by hypoxic, perinecrotic cells in GBM likely account for their tight association with necrosis and may be related to their poor prognosis.
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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.