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Plasma metabolomics offers a minimally invasive approach for identifying metabolic alterations that may provide insights into tumor progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We aimed to characterize plasma metabolomic profiles in patients with oral squamous cell carcinoma (OSCC) and evaluate their clinical relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Plasma samples from 43 OSCC patients and 129 cancer-free controls, matched at a 1:3 ratio based on age, sex, and body mass index, were analyzed using gas chromatography-mass spectrometry (GC-MS). A random forest algorithm was applied to identify key metabolic features distinguishing OSCC from controls. The clinical significance of the top metabolites was assessed and validated in another OSCC cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200927).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 113 compounds were putatively annotated and analyzed based on relative abundances. A ten-feature panel demonstrated good classification performance (area under the curve\u2009=\u20090.87; Matthews correlation coefficient\u2009=\u20090.703). The ten features are maltose, glucose, xylulose, \u03b4-gluconolactone, fructose, indoleacetic acid, \u03b1-hydroxybutyric acid, glutamic acid, cysteine, and the monoacylglyceride MG(18:1(9Z)\/0:0\/0:0), suggesting dysregulated carbohydrate metabolism and oxidative stress as the major plasma metabolomic alterations in OSCC. Notably, \u03b1-hydroxybutyric acid levels were elevated in patients with regional lymph node metastasis compared with those without.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings underscore the intricate interplay between altered glucose metabolism, redox imbalance, and OSCC. \u03b1-hydroxybutyric acid, a marker of oxidative stress and an indicator of insulin resistance, may be associated with metastatic progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11306-026-02431-7","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T12:42:30Z","timestamp":1776516150000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Linking metabolism and metastasis: elevated \u03b1-hydroxybutyric acid in oral squamous cell carcinoma patients with lymph node metastasis"],"prefix":"10.1007","volume":"22","author":[{"given":"Xiaolian","family":"Gu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Coates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Sgaramella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Magan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Nylander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"2431_CR1","doi-asserted-by":"publisher","unstructured":"Alapati, S., Fortuna, G., Ramage, G., & Delaney, C. 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