Abstract

Introduction Serum amino acid (AA) profiles represent a valuable tool in the metabolic assessment of cancer patients; still, information on the AA pattern in head and neck cancer (HNC) patients is insufficient. The aim of the study was to assess whether serum AA levels were associated with the stage of neoplastic disease and prognosis in primary HNC patients. Methods Two hundred and two primary HNC patients were included in the study. Thirty-one AAs and derivatives were measured in serum through an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). The association between AA concentrations and the stage (advanced versus early) of HNC was estimated using a multivariable logistic regression model. A multivariable Cox regression model was used to evaluate the prognostic significance of each AA. Results At the multivariable logistic regression analysis, increased levels of alpha-aminobutyric acid, aminoadipic acid, histidine, proline, and tryptophan were associated with a reduced risk of advanced stage HNC, while high levels of beta-alanine, beta-aminobutyric acid, ethanolamine, glycine, isoleucine, 4-hydroxyproline, and phenylalanine were associated with an increased risk of advanced stage HNC. Furthermore, at multivariate analysis, increased levels of alpha-aminobutyric acid were associated with increased overall survival (OS), while high levels of arginine, ethanolamine, glycine, histidine, isoleucine, 4-hydroxyproline, leucine, lysine, 3-methylhistidine, phenylalanine, and serine were associated with decreased OS. Conclusions Our study suggests that AA levels are associated with the stage of disease and prognosis in patients with HNC. More study is necessary to evaluate if serum AA levels may be considered a hallmark of HNC and prove to be clinically useful markers of disease status and prognosis in HNC patients.

Highlights

  • Serum amino acid (AA) profiles represent a valuable tool in the metabolic assessment of cancer patients; still, information on the AA pattern in head and neck cancer (HNC) patients is insufficient

  • The aim of this study was to quantitate a wider panel of serum AAs in primary HNC patients using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) in order to provide an expanded view of the associations between increased AA levels, stage of disease, and overall survival (OS)

  • High levels of alpha-aminobutyric acid (OR: 0.40; 95% CI: 0.160.98), aminoadipic acid (OR: 0.36; 95% CI: 0.17-0.78), histidine (OR: 0.40; 95% CI: 0.19-0.85), proline (OR: 0.24; 95% CI: 0.09-0.62), and tryptophan (OR: 0.41; 95% CI: 0.220.76) were associated with a reduced risk of advanced stage HNC, while high levels of beta-alanine (OR: 2.55; 95% CI: 1.17-5.60), beta-aminobutyric acid (OR: 1.91; 95% CI: 1.003.65), ethanolamine (OR: 2.25; 95% CI: 1.20-4.24), glycine (OR: 2.35; 95% CI: 1.17-4.73), isoleucine (OR: 2.39; 95% CI: 1.20-4.76), 4-hydroxyproline (OR: 3.16; 95% CI: 1.02-9.78), and phenylalanine (OR: 2.72; 95% CI: 1.42-5.21) were associated with an increased risk of advanced stage HNC

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Summary

Introduction

Serum amino acid (AA) profiles represent a valuable tool in the metabolic assessment of cancer patients; still, information on the AA pattern in head and neck cancer (HNC) patients is insufficient. The aim of the study was to assess whether serum AA levels were associated with the stage of neoplastic disease and prognosis in primary HNC patients. At the multivariable logistic regression analysis, increased levels of alpha-aminobutyric acid, aminoadipic acid, histidine, proline, and tryptophan were associated with a reduced risk of advanced stage HNC, while high levels of beta-alanine, beta-aminobutyric acid, ethanolamine, glycine, isoleucine, 4-hydroxyproline, and phenylalanine were associated with an increased risk of advanced stage HNC. Our study suggests that AA levels are associated with the stage of disease and prognosis in patients with HNC. More study is necessary to evaluate if serum AA levels may be considered a hallmark of HNC and prove to be clinically useful markers of disease status and prognosis in HNC patients. While HNC can be often cured when diagnosed at an early stage, late-stage disease may be untreatable or involves aggressive multimodality treatment that often leads to severe physical and psychological disabilities [6]

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