ORAL LEUKOPLAKIA WITH AND WITHOUT MALIGNANT TRANSFORMATION ARE METABOLICALLY DISTINCT

Abstract

<h3>Objectives</h3> To compare the metabolic profile of oral leukoplakia with and without malignant transformation. <h3>Study Design</h3> We evaluated samples of untransformed oral leukoplakia (<i>n</i> = 15) and those that underwent malignant transformation (<i>n</i> = 5) by high-performance liquid chromatography-mass spectrometry-based untargeted metabolomics. Univariate and multivariate statistical methods were applied to detect potentially discriminating compounds between groups. The mummichog and gene set enrichment analysis algorithms were associated to predict the enriched biological pathways. <h3>Results</h3> Seventy-two compounds were statistically significant (<i>P</i> < .05) for discriminating our study groups. Multivariate statistical analysis demonstrated the distinct metabolic profile of the samples, revealing a trend for the separation of transformed and untransformed oral leukoplakias. The main enriched pathways were related to lipid metabolism, synthesis of proinflammatory molecules, and retinoic and vitamin E metabolism. <h3>Conclusions</h3> The current results suggest untargeted metabolomics' potential to discriminate malignantly transformed leukoplakias from untransformed ones. Statistical analysis showed compounds that may characterize each evaluated group. Also, the enriched metabolic pathways were consistent with carcinogenesis-related processes. Further evaluation of the significantly altered compounds may be promising for developing a biomarker panel for the early diagnosis of leukoplakia with an increased risk of malignant progression.