ArticleThe American journal of pathology2010
HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 3 of them syntheses that pooled it.
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The trial behind it
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
152 citing papers in PubMed, 3 syntheses or guidelines pooled it, 282 citations in OpenAlex.
- The association between hypoxia inducible factor 1 subunit alpha gene rs2057482 polymorphism and cancer risk: a meta-analysis.BMC cancer · 2019Pooled it
- Clinicopathological and prognostic significance of hypoxia-inducible factor-1 alpha in lung cancer: a systematic review with meta-analysis.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2016Pooled it
- Prognostic value and clinicopathological differences of HIFs in colorectal cancer: evidence from meta-analysis.PloS one · 2013Pooled it
- Trial
- Article
- Glucose Metabolism Regulating Colorectal Cancer Initiation and Progression.Cancer science · 2026Review
- Transcriptomic and multi-layer variant analysis identifies STAT3 and HIF1A as central regulators of regulated cell death pathways in lung squamous cell carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Natural Products Targeting Angiogenesis and Tumor Microenvironment in Gastrointestinal Malignancies.Cells · 2026Review
- Role of the RBMS Family in Different Cancers and Research Progress.International journal of medical sciences · 2026Review
- High-fat diet driven post-operative colon cancer recurrence is dependent upon genetic susceptibility to deoxycholic acid.Cancer letters · 2025Article
- Hypoxia-Inducible Factor 1-alpha (HIF1α), Nicotinamide Adenine Dinucleotide (NAD+, NADH), and Nitric Oxide (NO) interplay in critically ill patients, with implications for patient safety and targeted therapies: a review.Patient safety in surgery · 2025Review
- Circulating tumor cells: mechanisms and clinical significance in colorectal cancer metastasis.Molecular cancer · 2025Review
- Emerging Strategies for Targeting Angiogenesis and the Tumor Microenvironment in Gastrointestinal Malignancies: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Linking microRNA to metabolic reprogramming and gut microbiota in the pathogenesis of colorectal cancer (Review).International journal of molecular medicine · 2025Review
- Natural Alternatives in the Treatment of Colorectal Cancer: A Mechanisms Perspective.Biomolecules · 2025Review
- Impact of HIF-1α, LOX and ITGA5 Synergistic Interaction in the Tumor Microenvironment on Colorectal Cancer Prognosis.Diagnostics (Basel, Switzerland) · 2025Article
- Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8.Nature communications · 2025Article
- Association between single nucleotide polymorphisms inFrontiers in genetics · 2025Article
- Prognostic implications of HIF-1α expression in anal squamous cell carcinoma treated with intensity-modulated radiotherapy (IMRT).Clinical and translational radiation oncology · 2024Article
- HIF-1 inactivation empowers HIF-2 to drive hypoxia adaptation in aggressive forms of medulloblastoma.Cell death discovery · 2024Article
92 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Tissue hypoxia commonly occurs in tumors. Hypoxia- inducible factor (HIF)-1 and HIF-2, which are essential mediators of cellular response to hypoxia, regulate gene expression for tumor angiogenesis, glucose metabolism, and resistance to oxidative stress. Their key regulatory subunits, HIF1A (HIF-1alpha) and endothelial PAS domain protein 1 (EPAS1; HIF-2alpha), are overexpressed and associated with patient prognosis in a variety of cancers. However, prognostic or molecular features of colon cancer with HIF expression remain uncertain. Among 731 colorectal cancers in two prospective cohort studies, 142 (19%) tumors showed HIF1A overexpression, and 322 (46%) showed EPAS1 overexpression by immunohistochemistry. HIF1A overexpression was significantly associated with higher colorectal cancer-specific mortality in Kaplan-Meier analysis (log-rank test, P < 0.0001), univariate Cox regression (hazard ratio = 1.84; 95% confidence interval, 1.37 to 2.47; P < 0.0001) and multivariate analysis (adjusted hazard ratio = 1.72; 95% confidence interval, 1.26 to 2.36; P = 0.0007) that adjusted for clinical and tumoral features, including microsatellite instability, TP53 (p53), PTGS2 (cyclooxygenase-2), CpG island methylator phenotype, and KRAS, BRAF, PIK3CA, and LINE-1 methylation. In contrast, EPAS1 expression was not significantly associated with patient survival. In addition, HIF1A expression was independently associated with PTGS2 expression (P = 0.0035), CpG island methylator phenotype-high (P = 0.013), and LINE-1 hypomethylation (P = 0.017). EPAS1 expression was inversely associated with high tumor grade (P = 0.0017) and obesity (body mass index > or = 30 kg/m2) (P = 0.039). In conclusion, HIF1A expression is independently associated with poor prognosis in colorectal cancer, suggesting HIF1A as a biomarker with potentially important therapeutic implications.
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