Salivary metabolic profile in patients with oral squamous cell carcinoma and potentially malignant disorders

Abstract

Oral Potential Malignant Lesions (OPMDs), including oral leukoplakia (OLK) and lichen planus (OLP), as well as Oral Squamous Cell Carcinoma (OSCC) are influenced by oral dysbiosis and might represent a disease continuum. Our hypothesis was that the oral salivary metabolomic reflects the association of those diseases. Hence, we aimed to study and compare salivary metabolites and metabolic pathways in OPMDs and OSCC. Unstimulated saliva samples were collected from 60 participants: OLK (n = 15), OLP (n = 15), OSCC (n = 15), and healthy controls (HCs; n = 15). Metabolites were quantified using NMR spectroscopy, and pathway analyses were performed with MetaboAnalyst 6.0. Four metabolites (acetate, taurine, pyruvate, methylamine) were elevated, while proline was consistently decreased in all disease groups relative to HCs. Four key pathways were altered: pyruvate metabolism (in all disease groups), glutamate metabolism (in OLK and OSCC), taurine and hypotaurine metabolism (in OLP and OLK), and the glucose–alanine cycle. OLK shared more metabolic features with OSCC than with OLP. Salivary metabolomic profiling reveals distinct metabolic alterations across OPMDs and OSCC, supporting their potential continuum and reflecting disease-related biochemical reprogramming. These findings highlight salivary metabolomics as a promising, non-invasive tool for understanding pathogenesis and for future development of biomarkers. Divergent metabolic pathways in OLP and OLK may relate to their different pathogenesis and malignant transformation risks. Improved understanding of these pathways may support early diagnostics and targeted therapeutic strategies.