ArticleFrontiers in genetics2022
A novel hypoxia-driven gene signature that can predict the prognosis and drug resistance of gliomas.
Article in Frontiers in genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- Therapeutic Potential of Tetrandrine Compared to Temozolomide in Treating Glioblastoma Multiforme Under Normoxic and Hypoxic Conditions.International journal of molecular sciences · 2026Article
- Drug resistance in glioblastoma: Challenges, mechanisms and therapeutic strategies (Review).Molecular and clinical oncology · 2026Review
- SKP2 protein as a prognostic biomarker for glioma and promotes tumor progression by regulating the cell cycle.Scientific reports · 2025Article
- Transcriptomic Profile of Isocitrate Dehydrogenase Mutant Type of Lower-Grade Glioma Reveals Molecular Changes for Prognosis.Biomedicines · 2025Article
- Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy.Cancer cell international · 2024Review
- Hypoxia-responsive geneJournal of Cancer · 2024Article
- Predictive value of a stemness-based classifier for prognosis and immunotherapy response of hepatocellular carcinoma based on bioinformatics and machine-learning strategies.Frontiers in immunology · 2024Article
- Drug resistance in glioblastoma: from chemo- to immunotherapy.Cancer drug resistance (Alhambra, Calif.) · 2023Review
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia spontaneously forms in the interior of glioma tissues and regulates the expression of various genes. However, the status of hypoxia-driven genes in glioma tissues is not completely known. In the current study, RNA-seq data of 695 glioma tissues in The Cancer Genome Atlas (TCGA) were set as a discovery cohort and were used to identify hypoxia-driven genes and construct a novel gene signature. The prognostic values of that signature were verified in data from the TCGA and the Chinese Glioma Genome Atlas (CGGA). The expression and diagnostic values of hypoxia-driven genes were analyzed using immunohistochemistry and receiver operator characteristic curves. Finally, the effects of hypoxia-driven genes on temozolomide (TMZ) resistance were analyzed by western blot, CCK-8 and colony formation assay. A total of 169 hypoxia-driven genes were identified, which were associated with a poor outcome in glioma patients. Among them, 22 genes had a degree score ≥10 and 6 genes (WT1, HOXA2, HOXC6, MMP9, SHOX2 and MYOD1) were selected to construct a signature to classify glioma patients into low- or high-risk groups. That signature had a remarkable prognostic value for glioma patients in TCGA and CGGA. The expression of HOXC6, MMP9, SHOX2 and MYOD1 was associated with hypoxia degree in glioma tissues and in recurrent cases, had a remarkable diagnostic value and a significant relationship with disease free survival in glioma patients. Moreover, SHOX2 was highly expressed in glioma tissues with O-6-methylguanine-DNA methyltransferase (MGMT)-unmethylation and temozolomide (TMZ) resistant glioma cell lines, and associated with MGMT expression. Knockdown the expression of SHOX2 significantly reduced the TMZ-resistance induced by hypoxia in glioma cells. Ultimately, we identified six novel hypoxia-driven genes for reliable prognostic prediction in gliomas and found that SHOX2 might be a potential target to overcome the TMZ resistance induced by hypoxia.
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