Salivary Metabolomics Discloses Metabolite Signatures of Oral Leukoplakia with and Without Dysplasia

Leukoplakia is a condition marked by white patches on the inner surfaces of the oral
cavity. Its potential to progress to oral squamous cell carcinoma underscores the need for
effective screening and early diagnosis procedures. We employed NMR-based salivary
and tissue metabolomics to identify potential biomarkers for leukoplakia and dysplastic
leukoplakia. Univariate and multivariate methods were used to evaluate the NMR-derived
metabolite concentrations. The salivary metabolite profile of leukoplakia exhibited specific
alterations compared to healthy controls. These metabolic changes were more pronounced
in cases of dysplastic lesions. Multivariate ROC curve analysis, based on a selection of
salivary metabolites, ascribed high diagnostic accuracy to the models that discriminate
between dysplastic and healthy cases. However, NMR analysis of tissue biopsies was
ineffective in extracting metabolic signatures to differentiate between lesional, peri-lesional,
and healthy tissues. Our pilot study employing a metabolomics-based approach led to
the development of salivary models that represent a complementary strategy for clinically
detecting leukoplakia. However, larger-scale validation is required to fully evaluate
their diagnostic potential and to effectively stratify leukoplakia patients according to
dysplasia status.