Comparative Analysis of Salivary Metabolomic Signatures in Oral Lichen Planus and Leukoplakia- A Cross-sectional study

Background:Oral lichen planus (OLP) and oral leukoplakia (OLK) are among the most prevalent oral potentially malignant disorders (OPMDs), yet they differ in biological behavior and malignant transformation risk. Metabolomic profiling of saliva offers a non-invasive method for detecting biochemical alterations that may discriminate between inflammatory and dysplastic lesions. Aim:To compare the salivary metabolomic signatures of OLP and OLK using capillary electrophoresistime-of-flight mass spectrometry (CE–TOF–MS) and to identify discriminatory metabolites with diagnostic potential. Materials and Methods:This cross-sectional comparative study included 60 participants: 20 with histopathologically confirmed OLP, 20 with OLK, and 20 healthy controls. Unstimulated whole saliva was collected, centrifuged, and stored at −80 °C. Metabolomic profiling was performed using CE–TOFMS, and metabolites were annotated with the Human Metabolome Database (HMDB). Multivariate statistical analyses (PCA, PLS-DA) and ROC curve modeling were used to identify discriminatory metabolites and assess diagnostic performance. Results:A total of 178 salivary metabolites were detected, of which 34 differed significantly between groups (p < 0.05). OLK exhibited upregulation of ornithine, indole-3-acetate, N-acetylglucosamine, and choline, whereas OLP showed higher putrescine, ethanolamine phosphate, and alanine levels. Pathway enrichment indicated disturbances in polyamine, amino acid, and choline metabolism. ROC analysis identified ornithine, indole-3-acetate, and putrescine as key discriminatory metabolites (AUC = 0.93, sensitivity 88%, specificity 85%). Conclusion:Salivary metabolomic profiling revealed distinct biochemical signatures between OLP and OLK. Elevated polyamine and choline metabolites in OLK reflect dysplastic metabolic reprogramming, whereas OLP shows an inflammatory metabolic phenotype. A combined salivary metabolite panel demonstrates high diagnostic accuracy, supporting saliva as a promising non-invasive biomarker source for differentiating oral potentially malignant disorders.