ArticleGenome biology2016
Genomic alterations underlie a pan-cancer metabolic shift associated with tumour hypoxia.
Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed.
- Pan-cancer multi-omics analysis identifies SYNGR4 as a novel clinical prognostic biomarker and therapeutic target in lung adenocarcinoma.Discover oncology · 2026Article
- Snhg18 promotes hypoxic pulmonary hypertension by enhancing glycolysis.Respiratory research · 2026Article
- SENP1 drives de novo cholesterogenesis via disrupting SUMOylation-mediated SREBP2-FBXW7 interaction.Cancer & metabolism · 2026Article
- Revolutionizing Breast Cancer Therapeutics: Intersecting Frontiers of Precision Medicine, Nanotechnology, and Drug Delivery Innovations.Current treatment options in oncology · 2025Review
- Landscape of metabolic alterations and treatment strategies in breast cancer.Genes & diseases · 2025Review
- Cell Settling, Migration, and Stochastic Cancer Gene Expression Suggest Potassium Membrane Flux May Initiate pH Reversal.Biomolecules · 2025Article
- Ginsenoside 20(S)-Rg3 upregulates SQLE to reprogram cholesterol metabolism of ovarian cancer cells.iScience · 2025Article
- Proteogenomic discovery ofScience advances · 2025Article
- Integrating Hypoxia Signatures from scRNA-seq and Bulk Transcriptomes for Prognosis Prediction and Precision Therapy in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma.International journal of molecular sciences · 2025Article
- Transcriptome Sequencing Reveals Effects of Artificial Feed Domestication on Intestinal Performance and Gene Expression of Carnivorous Mandarin Fish (Siniperca chuatsi) and Related Mechanisms.Marine biotechnology (New York, N.Y.) · 2025Article
- Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer.Cancer research · 2024Article
- Identification of Hypoxia-ALCAMAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Pathway-based signatures predict patient outcome, chemotherapy benefit and synthetic lethal dependencies in invasive lobular breast cancer.British journal of cancer · 2024Article
- NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer.World journal of gastrointestinal oncology · 2024Article
- Cone photoreceptor phosphodiesterase PDE6H inhibition regulates cancer cell growth and metabolism, replicating the dark retina response.Cancer & metabolism · 2024Article
- Exploring the relationship between metabolism and immune microenvironment in osteosarcoma based on metabolic pathways.Journal of biomedical science · 2024Article
- Metabolic stratification of human breast tumors reveal subtypes of clinical and therapeutic relevance.iScience · 2023Article
- Repurposing antifungal drugs for cancer therapy.Journal of advanced research · 2023Review
- Hypoxia truncates and constitutively activates the key cholesterol synthesis enzyme squalene monooxygenase.eLife · 2023Article
- Expression and kinetic characterization of PYCR3.Archives of biochemistry and biophysics · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
backgroundAltered metabolism is a hallmark of cancer. However, the role of genomic changes in metabolic genes driving the tumour metabolic shift remains to be elucidated. Here, we have investigated the genomic and transcriptomic changes underlying this shift across ten different cancer types.
resultsA systematic pan-cancer analysis of 6538 tumour/normal samples covering ten major cancer types identified a core metabolic signature of 44 genes that exhibit high frequency somatic copy number gains/amplifications (>20 % cases) associated with increased mRNA expression (ρ > 0.3, q < 10(-3)). Prognostic classifiers using these genes were confirmed in independent datasets for breast and kidney cancers. Interestingly, this signature is strongly associated with hypoxia, with nine out of ten cancer types showing increased expression and five out of ten cancer types showing increased gain/amplification of these genes in hypoxic tumours (P ≤ 0.01). Further validation in breast and colorectal cancer cell lines highlighted squalene epoxidase, an oxygen-requiring enzyme in cholesterol biosynthesis, as a driver of dysregulated metabolism and a key player in maintaining cell survival under hypoxia.
conclusionsThis study reveals somatic genomic alterations underlying a pan-cancer metabolic shift and suggests genomic adaptation of these genes as a survival mechanism in hypoxic tumours.
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