GLOBAL PROTEOMIC PROFILING REVEALS METABOLIC REPROGRAMMING IN AMELOBLASTOMAS

Abstract

<h3>Objectives</h3> To compare the proteome of ameloblastomas and dental follicles. <h3>Study Design</h3> We performed liquid chromatography-tandem mass spectrometry in tumor-enriched samples. Protein-protein interaction network, KEGG-enriched pathways, and gene ontology analyses of differentially abundant proteins were performed. To investigate the activation of the antioxidant system, we assessed the immunoexpression of the glutathione-S-transferase omega-1 (GSTO1). We also examined the status of BRAF mutation in the tumor cases. Statistical analysis was performed using Perseus software. <h3>Results</h3> Ameloblastomas were shown to harbor a proteomic profile distinct from that found in dental follicles, with 33 overregulated and 21 downregulated proteins. Overregulated proteins are involved in glucose metabolism and biosynthesis pathways. Most of the downregulated proteins play prominent roles in cellular mitochondrial energy production and oxidoreductase metabolism regulation. BRAF P.V600E was detected in most ameloblastomas. Ameloblastomas showed diffuse and moderate to strong GSTO1 immunoexpression, whereas weak or negative immunoexpression was observed in dental follicles. <h3>Conclusions</h3> We were able to identify alterations in critical metabolic pathways for the first time, which not only contributes to the elucidation of ameloblastoma pathogenesis but also could be potential targets for drug therapy in these tumors.