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- Title
HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma.
- Authors
Fleming, Jason C.; Woo, Jeongmin; Moutasim, Karwan; Mellone, Massimiliano; Frampton, Steven J.; Mead, Abbie; Ahmed, Waseem; Wood, Oliver; Robinson, Hollie; Ward, Matthew; Woelk, Christopher H.; Ottensmeier, Christian H.; King, Emma; Kim, Dae; Blaydes, Jeremy P.; Thomas, Gareth J.
- Abstract
<bold>Background: </bold>Metabolic changes in tumour cells are used in clinical imaging and may provide potential therapeutic targets. Human papillomavirus (HPV) status is important in classifying head and neck cancers (HNSCC), identifying a distinct clinical phenotype; metabolic differences between these HNSCC subtypes remain poorly understood.<bold>Methods: </bold>We used RNA sequencing to classify the metabolic expression profiles of HPV+ve and HPV-ve HNSCC, performed a meta-analysis on FDG-PET imaging characteristics and correlated results with in vitro extracellular flux analysis of HPV-ve and HPV+ve HNSCC cell lines. The monocarboxylic acid transporter-1 (MCT1) was identified as a potential metabolic target and tested in functional assays.<bold>Results: </bold>Specific metabolic profiles were associated with HPV status, not limited to carbohydrate metabolism. There was dominance of all energy pathways in HPV-negative disease, with elevated expression of genes associated with glycolysis and oxidative phosphorylation. In vitro analysis confirmed comparative increased rates of oxidative phosphorylation and glycolysis in HPV-negative cell lines. PET SUV(max) scores however were unable to reliably differentiate between HPV-positive and HPV-negative tumours. MCT1 expression was significantly increased in HPV-negative tumours, and inhibition suppressed tumour cell invasion, colony formation and promoted radiosensitivity.<bold>Conclusion: </bold>HPV-positive and negative HNSCC have different metabolic profiles which may have potential therapeutic applications.
- Publication
British Journal of Cancer, 2019, Vol 120, Issue 3, p356
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-018-0364-7