Perfil de metilação e expressão do gene CDKN2a em carcinoma epidermóide oral
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
Texto Completo: | http://repositorio.ufes.br/handle/10/7126 |
Resumo: | 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. |
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Von Zeidler, Sandra VentorinEduardo, Vinicius MendesPaula, Flávia deMendonça, Elismauro Francisco de2018-08-01T21:35:05Z2018-08-012018-08-01T21:35:05Z2018-03-19Determination 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.Determinação e validação de biomarcadores tumorais são importantes para avaliar o prognóstico de pacientes com câncer. Este estudo teve como objetivo avaliar o perfil de metilação e de expressão do gene CDKN2a como possível a biomarcador de prognóstico em pacientes com carcinoma epidermóide oral (CEO). Foram selecionados 115 casos com diagnóstico conclusivo de CEO destes 70 apresentavam tecido tumoral congelado. Dados clínico-patológicos foram obtidos por meio de entrevista e análise de prontuários. Cinquenta e cinco amostras de DNA com qualidade obtidas foram submetidas a PCR específica para metilação, e os casos positivos foram submetidos ao sequenciamento de Sanger para avaliar os dinucleotídeos citosina-guanina hipermetilados. Expressão da proteína p16 foi avaliada por imunohistoquímica. As análises estatísticas relacionando os resultados foram feitas e as curvas de Sobrevida Global e Sobrevida Livre de Doença foram elaboradas pelo método de Kaplan-Meier. A frequência de hipermetilação do CDKN2a na população estudada foi de 36,4%, sendo que a maior parte das citosinas localizadas em regiões CpG estavam hipermetiladas e citosinas fora da região CG também apresentaram metilação. A expressão de p16 foi predominantemente baixa (76,7%) nestas amostras. O perfil de metilação não mostrou associação com os indicadores de prognóstico, bem como não interferiu na Sobrevida Global e Livre de Doença. No entanto, os indicadores de prognóstico tamanho do tumor, estádio clínico, metástase linfonodal e modalidade de tratamento mostraram estar associados à Sobrevida Global. Concluímos que a hipermetilação do gene CDKN2a não se mostrou um bom biomarcador de prognóstico no grupo analisado neste estudo, mas parece desempenhar papel importante na carcinogênese do CEO.Texthttp://repositorio.ufes.br/handle/10/7126porUniversidade Federal do Espírito SantoMestrado em BiotecnologiaPrograma de Pós-Graduação em BiotecnologiaUFESBRCentro de Ciências da SaúdeHypermethylationEpigeneticsOral cavityHipermetilaçãoP16EpigenéticaCavidade bucalGenesCâncerBiotecnologia farmacêuticaBiotecnologia61Perfil de metilação e expressão do gene CDKN2a em carcinoma epidermóide oralinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFESORIGINALtese_12339_Dissertação_Vinicius Mendes Eduardo.pdfapplication/pdf1080730http://repositorio.ufes.br/bitstreams/40699e95-6dc6-43e7-afa2-8cade5f58e0b/download5a5942cebcb4a270d6c8129b73cfc107MD5110/71262024-06-27 11:08:33.895oai:repositorio.ufes.br:10/7126http://repositorio.ufes.brRepositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestopendoar:21082024-06-27T11:08:33Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)false |
dc.title.none.fl_str_mv |
Perfil de metilação e expressão do gene CDKN2a em carcinoma epidermóide oral |
title |
Perfil de metilação e expressão do gene CDKN2a em carcinoma epidermóide oral |
spellingShingle |
Perfil de metilação e expressão do gene CDKN2a em carcinoma epidermóide oral Eduardo, Vinicius Mendes Hypermethylation Epigenetics Oral cavity Hipermetilação P16 Epigenética Cavidade bucal Biotecnologia Genes Câncer Biotecnologia farmacêutica 61 |
title_short |
Perfil de metilação e expressão do gene CDKN2a em carcinoma epidermóide oral |
title_full |
Perfil de metilação e expressão do gene CDKN2a em carcinoma epidermóide oral |
title_fullStr |
Perfil de metilação e expressão do gene CDKN2a em carcinoma epidermóide oral |
title_full_unstemmed |
Perfil de metilação e expressão do gene CDKN2a em carcinoma epidermóide oral |
title_sort |
Perfil de metilação e expressão do gene CDKN2a em carcinoma epidermóide oral |
author |
Eduardo, Vinicius Mendes |
author_facet |
Eduardo, Vinicius Mendes |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Von Zeidler, Sandra Ventorin |
dc.contributor.author.fl_str_mv |
Eduardo, Vinicius Mendes |
dc.contributor.referee1.fl_str_mv |
Paula, Flávia de |
dc.contributor.referee2.fl_str_mv |
Mendonça, Elismauro Francisco de |
contributor_str_mv |
Von Zeidler, Sandra Ventorin Paula, Flávia de Mendonça, Elismauro Francisco de |
dc.subject.eng.fl_str_mv |
Hypermethylation Epigenetics Oral cavity |
topic |
Hypermethylation Epigenetics Oral cavity Hipermetilação P16 Epigenética Cavidade bucal Biotecnologia Genes Câncer Biotecnologia farmacêutica 61 |
dc.subject.por.fl_str_mv |
Hipermetilação P16 Epigenética Cavidade bucal |
dc.subject.cnpq.fl_str_mv |
Biotecnologia |
dc.subject.br-rjbn.none.fl_str_mv |
Genes Câncer Biotecnologia farmacêutica |
dc.subject.udc.none.fl_str_mv |
61 |
description |
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. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-08-01T21:35:05Z |
dc.date.available.fl_str_mv |
2018-08-01 2018-08-01T21:35:05Z |
dc.date.issued.fl_str_mv |
2018-03-19 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufes.br/handle/10/7126 |
url |
http://repositorio.ufes.br/handle/10/7126 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
dc.format.none.fl_str_mv |
Text |
dc.publisher.none.fl_str_mv |
Universidade Federal do Espírito Santo Mestrado em Biotecnologia |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Biotecnologia |
dc.publisher.initials.fl_str_mv |
UFES |
dc.publisher.country.fl_str_mv |
BR |
dc.publisher.department.fl_str_mv |
Centro de Ciências da Saúde |
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Universidade Federal do Espírito Santo Mestrado em Biotecnologia |
dc.source.none.fl_str_mv |
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