Abstract

Introduction Differential expression of genes encoding cytochrome P450 (CYP) and other oxygenases enzymes involved in biotransformation mechanisms of endogenous and exogenous compounds can lead to oral tumor development. Objective We aimed to identify the expression profile of these genes, searching for susceptibility biomarkers in oral squamous cell carcinoma. Patients and Methods Sixteen oral squamous cell carcinoma samples were included in this study (eight tumor and eight adjacent non-tumor tissues). Gene expression quantification was performed using TaqMan Array Human CYP450 and other Oxygenases 96-well plate (Applied Biosystems) by real time qPCR. Protein quantification was performed by ELISA and IHC methods. Bioinformatics tools were used to find metabolic pathways related to the enzymes encoded by differentially expressed genes. Results. CYP27B1, CYP27A1, CYP2E1, CYP2R1, CYP2J2, CYP2U1, CYP4F12, CYP4X1, CYP4B1, PTGIS, ALOX12, and MAOB genes presented differential expression in the oral tumors. After correction by multiple tests, only the PTGIS (Prostaglandin I2 Synthase) gene presented significant differential expression (P < 0.05). The PTGIS gene and protein were reduced in oral tumors. Conclusion PTGIS presents downexpression in oral tumors. PTGIS play an important role in the arachidonic acid metabolism. Arachidonic acid and/or metabolites are derived from this pathway, which can influence the regulation of important physiological mechanisms in tumorigenesis process.

Highlights

  • Differential expression of genes encoding cytochrome P450 (CYP) and other oxygenases enzymes involved in biotransformation mechanisms of endogenous and exogenous compounds can lead to oral tumor development

  • 12 pathways were associated with the carcinogenesis process, highlighting the arachidonic acid metabolism, in which five of the differentially expressed genes in oral squamous cell carcinoma (OSCC) (ALOX12, CYP2E1, CYP2J2, CYP2U1, and PTGIS) act

  • Because the role of arachidonic acid metabolism was representative in this study, the proteins encoded by these genes were selected for protein analysis by Enzyme-Linked Immunosorbent Assay (ELISA) and IHC [47]

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Summary

Introduction

Differential expression of genes encoding cytochrome P450 (CYP) and other oxygenases enzymes involved in biotransformation mechanisms of endogenous and exogenous compounds can lead to oral tumor development. We aimed to identify the expression profile of these genes, searching for susceptibility biomarkers in oral squamous cell carcinoma. Bioinformatics tools were used to find metabolic pathways related to the enzymes encoded by differentially expressed genes. CYP27B1, CYP27A1, CYP2E1, CYP2R1, CYP2J2, CYP2U1, CYP4F12, CYP4X1, CYP4B1, PTGIS, ALOX12, and MAOB genes presented differential expression in the oral tumors. After correction by multiple tests, only the PTGIS (Prostaglandin I2 Synthase) gene presented significant differential expression (P < 0.05). The PTGIS gene and protein were reduced in oral tumors. Approximately 600,000 new cases of head and neck cancer HNC are diagnosed each year, and oral cancer comprises about half of these cases and is considered the most representative site of this tumor type [1]. It was estimated that there are 3,500 new cases [2]

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