HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma

头颈部鳞状细胞癌中的 HPV、肿瘤代谢和新靶点识别

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作者:Jason C Fleming, Jeongmin Woo, Karwan Moutasim, Massimiliano Mellone, Steven J Frampton, Abbie Mead, Waseem Ahmed, Oliver Wood, Hollie Robinson, Matthew Ward, Christopher H Woelk, Christian H Ottensmeier, Emma King, Dae Kim, Jeremy P Blaydes, Gareth J Thomas

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.

Conclusion

HPV-positive and negative HNSCC have different metabolic profiles which may have potential therapeutic applications.

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

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.

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