ArticlePloS one2015
A combined gene signature of hypoxia and notch pathway in human glioblastoma and its prognostic relevance.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- Transcriptome analysis of goat adipose tissue-derived mesenchymal stem cells cultured in variable oxygen conditions.Frontiers in cell and developmental biology · 2026Article
- Spatial transcriptomics of glioblastoma defines biologically and clinically significant reprogramming patterns across unique spatial microenvironments.bioRxiv : the preprint server for biology · 2025Article
- Pan-cancer analysis reveals dual roles of HES6 in cancer immunity and prognosis.Discover oncology · 2025Article
- Genomic, epigenomic and transcriptomic landscape of glioblastoma.Metabolic brain disease · 2024Review
- Review
- Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma.International journal of molecular sciences · 2023Review
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
- PGK1 : An Essential Player in Modulating Tumor Metabolism.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Article
- Regulatory Network of PD1 Signaling Is Associated with Prognosis in Glioblastoma Multiforme.Cancer research · 2021Article
- Proteomics-based prognostic signature and nomogram construction of hypoxia microenvironment on deteriorating glioblastoma (GBM) pathogenesis.Scientific reports · 2021Article
- Review
- Hypoxia Activates Notch4 via ERK/JNK/P38 MAPK Signaling Pathways to Promote Lung Adenocarcinoma Progression and Metastasis.Frontiers in cell and developmental biology · 2021Article
- Contradictory Effect of Notch1 and Notch2 on Phosphatase and Tensin Homolog and its Influence on Glioblastoma Angiogenesis.Galen medical journal · 2021Article
- Phosphoglycerate kinase: structural aspects and functions, with special emphasis on the enzyme from Kinetoplastea.Open biology · 2020Review
- Hypoxia-induced epithelial to mesenchymal transition in cancer.Cancer letters · 2020Review
- An eight-mRNA signature outperforms the lncRNA-based signature in predicting prognosis of patients with glioblastoma.BMC medical genetics · 2020Article
- Article
- Review
- PGK1-mediated cancer progression and drug resistance.American journal of cancer research · 2019Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia is a hallmark of solid tumors including glioblastoma (GBM). Its synergism with Notch signaling promotes progression in different cancers. However, Notch signaling exhibits pleiotropic roles and the existing literature lacks a comprehensive understanding of its perturbations under hypoxia in GBM with respect to all components of the pathway. We identified the key molecular cluster(s) characteristic of the Notch pathway response in hypoxic GBM tumors and gliomaspheres. Expression of Notch and hypoxia genes was evaluated in primary human GBM tissues by q-PCR. Clustering and statistical analyses were applied to identify the combination of hypoxia markers correlated with upregulated Notch pathway components. We found well-segregated tumor-clusters representing high and low HIF-1α/PGK1-expressors which accounted for differential expression of Notch signaling genes. In combination, a five-hypoxia marker set (HIF-1α/PGK1/VEGF/CA9/OPN) was determined as the best predictor for induction of Notch1/Dll1/Hes1/Hes6/Hey1/Hey2. Similar Notch-axis genes were activated in gliomaspheres, but not monolayer cultures, under moderate/severe hypoxia (2%/0.2% O2). Preliminary evidence suggested inverse correlation between patient survival and increased expression of constituents of the hypoxia-Notch gene signature. Together, our findings delineated the Notch-axis maximally associated with hypoxia in resected GBM, which might be prognostically relevant. Its upregulation in hypoxia-exposed gliomaspheres signify them as a better in-vitro model for studying hypoxia-Notch interactions than monolayer cultures.
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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.