Regional HNSCC metabolomics reveals widespread changes to one-carbon metabolism and S-adenosylmethionine metabolism across tumour core, tumour edge and adjacent non-tumour tissues
Menée à partir de l'analyse métabolomique d'échantillons tumoraux et d'échantillons tissulaires adjacents normaux prélevés sur des patients atteints d'un cancer de la tête et du cou, cette étude met en évidence d'importantes modifications intratumorales du métabolisme monocarboné et du métabolisme de la S-adénosylméthionine
Background : Cancer, including head and neck squamous cell carcinoma (HNSCC), induces changes to metabolism that drive the disease. Regional metabolomics allows understanding of metabolic variation across the tumour, including in the tumour core, where hypoxia is likely more pronounced.
Methods : Ultra-high performance liquid chromatography-mass spectrometry metabolomics was applied to regionally distinct patient tissue samples: tumour edge, tumour core and adjacent non-tumour. Statistical, correlation and pathway enrichment analyses were performed.
Results : Markers of hypoxia or pseudohypoxia—lactate, succinate, fumarate, and the lactate:pyruvate ratio—were elevated in both core and edge tumour regions relative to adjacent tissue, with a trend toward stronger changes in the core. One-carbon metabolites were altered in HNSCC, including tumour-associated increases of S-adenosylmethionine (SAM) and SAM metabolites (S-adenosylhomocysteine, polyamines, methylated nucleosides, dimethylarginine, trimethylysine and 1-methylnicotinamide). Histidine, tryptophan, choline and folate appear metabolically connected to one-carbon metabolism in HNSCC: histidine, L-kynurenine (tryptophan metabolite), some purine metabolites (including deoxyguanosine, deoxyinosine) and choline were elevated in tumour tissue; while histidine/SAM, L-kynurenine/deoxyguanosine, L-kynurenine/deoxyinosine and folate/methionine were correlated in tumour tissue only.
Conclusion : Tumour edge and core exhibited one-carbon metabolic changes relative to non-tumour, with the magnitude of change generally greater in the core reflecting location dependent variation of SAM metabolism in HNSCC.
British Journal of Cancer , article en libre accès, 2026