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Introduction <p>Metabolic reprogramming is a hallmark of cancer. Plasma metabolomics offers a minimally invasive approach for identifying metabolic alterations that may provide insights into tumor progression.</p> Objectives <p>We aimed to characterize plasma metabolomic profiles in patients with oral squamous cell carcinoma (OSCC) and evaluate their clinical relevance.</p> Methods <p>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 (<i>n</i> = 27).</p> Results <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 = 0.87; Matthews correlation coefficient = 0.703). The ten features are maltose, glucose, xylulose, δ-gluconolactone, fructose, indoleacetic acid, α-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, α-hydroxybutyric acid levels were elevated in patients with regional lymph node metastasis compared with those without.</p> Conclusion <p>Our findings underscore the intricate interplay between altered glucose metabolism, redox imbalance, and OSCC. α-hydroxybutyric acid, a marker of oxidative stress and an indicator of insulin resistance, may be associated with metastatic progression.</p>

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Linking metabolism and metastasis: elevated α-hydroxybutyric acid in oral squamous cell carcinoma patients with lymph node metastasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月18日

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  • Xiaolian Gu,
  • Philip J. Coates,
  • Lixiao Wang,
  • Nicola Sgaramella,
  • Mustafa Magan,
  • Karin Nylander

摘要

Introduction

Metabolic reprogramming is a hallmark of cancer. Plasma metabolomics offers a minimally invasive approach for identifying metabolic alterations that may provide insights into tumor progression.

Objectives

We aimed to characterize plasma metabolomic profiles in patients with oral squamous cell carcinoma (OSCC) and evaluate their clinical relevance.

Methods

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 = 27).

Results

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 = 0.87; Matthews correlation coefficient = 0.703). The ten features are maltose, glucose, xylulose, δ-gluconolactone, fructose, indoleacetic acid, α-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, α-hydroxybutyric acid levels were elevated in patients with regional lymph node metastasis compared with those without.

Conclusion

Our findings underscore the intricate interplay between altered glucose metabolism, redox imbalance, and OSCC. α-hydroxybutyric acid, a marker of oxidative stress and an indicator of insulin resistance, may be associated with metastatic progression.