Head and/or Neck Cancer Deviates the Tryptophan, Arginine and Glutamine Pathways: Applications in Diagnosis and Prognosis

Background: This study aimed to identify metabolic alterations in the tryptophan, arginine, and glutamine pathways in patients with head and neck carcinoma (HNC) that could provide diagnostic and prognostic biomarkers.Materials and methods: Serum levels of tryptophan, kynurenine, arginine, putrescine, glutamate, and glutamine were measured using micellar electrokinetic chromatography with laser-induced fluorescence detection (MEKC-LIFD). The study cohort included five treatment-naïve HNC patients, four treated HNC patients, three patients with benign tumors, and seven healthy controls.Results: Serum concentrations of tryptophan and kynurenine were significantly elevated in both untreated and treated HNC patients compared to controls (p = 0.01 and p = 0.002, respectively). While both metabolites remained elevated post-treatment compared to controls (p = 0.002 and p = 0.0003, respectively), tryptophan decreased significantly after treatment. Serum arginine was significantly higher in patient groups versus controls (p = 0.04 and p = 0.002) but did not change with treatment. In contrast, serum putrescine increased after treatment compared to both controls (p = 0.035) and untreated patients (p = 0.05). The arginine/putrescine ratio was significantly lower in untreated versus treated patients. Furthermore, untreated HNC patients exhibited a significant decrease in glutamine and a significant increase in glutamate, a finding not present in treated patients. Serum glutamate was also elevated in benign tumor patients (p = 0.04).Conclusion: These findings reveal significant dysregulation of tryptophan metabolism in HNC and identify serum tryptophan and putrescine as potential markers for monitoring treatment efficacy. Altered arginine metabolism and a pronounced shift in the glutamine-glutamate axis, indicative of increased glutaminolysis, further characterize the metabolic profile of active HNC tumors.