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Regional metabolomics allows understanding of metabolic variation across the tumour, including in the tumour core, where hypoxia is likely more pronounced.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Markers of hypoxia or pseudohypoxia\u2014lactate, succinate, fumarate, and the lactate:pyruvate ratio\u2014were 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-026-03410-4","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T18:29:30Z","timestamp":1777487370000},"page":"372-381","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Regional HNSCC metabolomics reveals widespread changes to one-carbon metabolism and S-adenosylmethionine metabolism across tumour core, tumour edge and adjacent non-tumour tissues"],"prefix":"10.1038","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3030-7663","authenticated-orcid":false,"given":"Andrew D.","family":"Southam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6913-1557","authenticated-orcid":false,"given":"James A.","family":"Higginson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7989-6695","authenticated-orcid":false,"given":"Gavin R.","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7357-2670","authenticated-orcid":false,"given":"Matthew J.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1307-2102","authenticated-orcid":false,"given":"Lauren E.","family":"Cruchley-Fuge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Spruce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0132-8668","authenticated-orcid":false,"given":"Ossama","family":"Edbali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8796-4771","authenticated-orcid":false,"given":"Ralf J. 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