HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma
Menée in vitro et à partir notamment du séquençage de l'ARN messager de 39 échantillons tumoraux prélevés sur des patients atteints d'un carcinome épidermoïde de la tête et du cou, cette étude analyse, en fonction de la présence ou non d'une infection par le papillomavirus humain, le profil métabolique des cellules tumorales et identifie une nouvelle cible thérapeutique
Background : 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.
Methods : 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.
Results : 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.
Conclusion : HPV-positive and negative HNSCC have different metabolic profiles which may have potential therapeutic applications.
British Journal of Cancer , article en libre accès, 2019