Salivary monoacetylated polyamines as noninvasive biomarkers for early detection and stratification of oral squamous cell carcinoma: A targeted metabolomics study

Arch Oral Biol. 2026 Apr:184:106513. doi: 10.1016/j.archoralbio.2026.106513. Epub 2026 Jan 9.

Abstract

Objectives: This study aimed to evaluate salivary monoacetylated polyamines as noninvasive biomarkers for the detection and staging of oral squamous cell carcinoma (OSCC).

Design: Unstimulated saliva samples were collected from healthy controls (n = 15), oral leukoplakia (OLK) patients (n = 15), and OSCC patients stratified into early (n = 28) and advanced stages (n = 46). Seven polyamines were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Diagnostic performance was assessed via receiver operating characteristic (ROC) analysis, logistic regression modeling, and multivariate clustering.

Results: N1-acetylspermidine and N1-acetylspermine showed progressive elevation from OLK to advanced OSCC, with AUCs of 0.87 and 0.81, respectively. A two-marker logistic model achieved a cross-validated AUC of 0.85, demonstrating good discriminatory performance between malignant and non-malignant states. Multivariate analysis confirmed their contribution to disease stratification, while calibration plots supported model reliability.

Conclusions: Salivary N1-acetylspermidine and N1-acetylspermine are promising biomarkers for noninvasive OSCC detection and staging.

Keywords: Early detection; LC-MS/MS; Metabolomics; Oral squamous cell carcinoma; Polyamines; Salivary biomarkers.

MeSH terms

  • Acetylation
  • Adult
  • Aged
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / metabolism
  • Carcinoma, Squamous Cell* / diagnosis
  • Carcinoma, Squamous Cell* / metabolism
  • Carcinoma, Squamous Cell* / pathology
  • Case-Control Studies
  • Chromatography, Liquid
  • Early Detection of Cancer / methods
  • Female
  • Humans
  • Leukoplakia, Oral / diagnosis
  • Leukoplakia, Oral / metabolism
  • Male
  • Metabolomics*
  • Middle Aged
  • Mouth Neoplasms* / diagnosis
  • Mouth Neoplasms* / metabolism
  • Mouth Neoplasms* / pathology
  • Neoplasm Staging
  • Polyamines* / analysis
  • Polyamines* / metabolism
  • ROC Curve
  • Saliva* / chemistry
  • Saliva* / metabolism
  • Spermidine / analogs & derivatives
  • Spermidine / analysis
  • Spermidine / metabolism
  • Spermine / analogs & derivatives
  • Spermine / analysis
  • Spermine / metabolism
  • Tandem Mass Spectrometry

Substances

  • Biomarkers, Tumor
  • Polyamines
  • Spermine
  • Spermidine