Regional HNSCC metabolomics reveals widespread changes to one-carbon metabolism and S-adenosylmethionine metabolism across tumour core, tumour edge and adjacent non-tumour tissues

ABSTRACT:

Cancer, including head and neck squamous cell carcinoma (HNSCC), induces changes to metabolism that drive the disease. Regional metabolomics can help to understand metabolic variation across the tumour including changes near the tumour core, where hypoxia is likely more pronounced. We apply ultra-high performance liquid chromatography-mass spectrometry metabolomics to regionally distinct patient tissue samples: tumour edge, tumour core and adjacent non-tumour. Statistical, correlation and pathway enrichment analyses were performed. 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. Tumour edge and core exhibited similar one-carbon metabolic changes relative to non-tumour, but the magnitude of change was generally greater in the core reflecting location dependent variation of SAM metabolism in HNSCC.

INSTRUMENT(S): Liquid Chromatography MS - positive - hilic, Liquid Chromatography MS - negative - hilic

PROVIDER: MTBLS1905 | MetaboLights | 2026-06-03

REPOSITORIES: MetaboLights