Avaliação do polimorfismo do gene LEPR e do perfil de metilação da E-caderina em displasia de mucosa bucal e em carcinoma de células escamosas de boca

Abstract

This study aimed to evaluate the genetic polymorphism LEPR and the methylation profile of E-cadherin in dysplastic oral mucosa and oral squamous cell carcinoma (OSCC). The first objective was to analyze the genetic polymorphism LEPR gene is associated with the OSCC. To do this we evaluate Gln223Arg LEPR polymorphic variants of the gene in OSCC and epithelial dysplasia (ED), relative to the normal oral mucosa. The analysis of polymorphic variants of the gene were compared LEPR by PCR in 25 samples of potentially malignantly injury, OSCC 25 samples and 89 samples from patients without potentially malignantly lesions and / or OSCC. The frequency of GG genotype was approximately twice as often in patients with OSCC than in the control group. However, the A allele in its homozygous form (Gln223Gln), was significantly associated with the development of potentially malignantly injury, with 80% of the samples had AA genotype. The second objective was to examine whether hypoxic conditions induces the methylation of E-cadherin, thus reducing the expression of same in OSCC and dysplastic oral mucosa, compared to normal oral mucosa. For this, they used samples of cryopreserved oral squamous cell carcinoma (OSCC) (n = 35), samples of dysplastic oral mucosa (n = 18) and normal oral mucosa (n = 15). Further, immortalized cell lines (HaCat and SCC9) were subjected to hypoxic treatment, followed by methylation profile analysis (MS-PCR) and expression of mRNA (qPCR) of E-cadherin. The methylation profile analysis in groups of OSCC and dysplastic oral mucosa, showed that this is not a separate event between these groups of lesions. However, analysis of mRNA expression of E-cadherin in the lines of immortalized cells showed a significant decrease in expression of this gene under hypoxic condition compared to the control group, regardless of the methylation profile.