Perfil de metilação e expressão do gene CDKN2a em carcinoma epidermóide oral

Abstract

Determination and validation of tumor biomarkers are important to evaluate the prognosis of cancer patients. This study aimed to evaluate the methylation and expression profile of the CDKN2a gene as a possible prognostic biomarker in patients with oral squamous cell carcinoma (OSCC). We selected 115 cases with conclusive diagnosis of OSCC of these 70 with frozen tumor tissue available. Clinical-pathological data were obtained by interview and analysis of medical records. Fifty-five quality DNA samples were obtained and submitted to methylation-specific PCR, and the positive cases were submitted to Sanger sequencing to evaluate hypermethylated cytosineguanine dinucleotides. Expression of the p16 protein was assessed by immunohistochemistry. Statistical analyzes relating the results were made and the Global Survival and Disease-Free Survival curves were elaborated using the KaplanMeier method. The frequency of hypermethylation of CDKN2a in the study population was 36.4%, and most of the cytosines located in CpG regions were hypermethylated and cytosines outside the CG region also presented methylation. The expression of p16 was predominantly low (76.7%) in these samples. The methylation profile showed no association with the prognostic indicators, nor did it interfere with the Global and Disease-Free Survival. However, prognostic indicators of tumor size, clinical stage, lymph node metastasis and modality of treatment were shown to be associated with Global Survival. We conclude that the hypermethylation of the CDKN2a gene did not prove to be a good prognostic biomarker in the group analyzed in this study, but it seems to play an important role in the early stages of OSCC's carcinogenesis.