Análise da metilação dos genes SOX17, DKK3 e SFRP2, tipos de HPV e associação com a origem e o estadiamento do câncer de colo uterino
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2017-08-08
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Universidade Federal de Goiás
Resumo
Cervical cancer is caused by persistent high-risk HPV infection. In addition, genetic and
epigenetic changes such as the silencing of Wnt signaling pathway inhibitor genes appear to be
essential for the development and progression of the disease. This study aimed to analyze the
prevalence of HPV infections in cervical cancer and to verify the associations between age,
histological type, degree of tumor differentiation and the presence of methylation DKK3, SOX17
and SFRP2. This is a cross-sectional study including cases of cervical cancer, distributed in
diagnoses of squamous cell carcinomas and adenocarcinomas. The samples were assayed for
25 HPV genotypes using the INNOLipa® kit, then performed M-PCR to identify the presence of
methylation in the promoter region of the genes DKK3, SOX17 and SFRP2. The results of the
research showed that the age is significantly lower for women with cervical adenocarcinomas
compared to those with a diagnosis of squamous cell carcinoma. Infections with genotypes 18
and 45 were associated with the diagnosis of adenocarcinomas in women younger than 50
years. Methylation of inhibitors of the Wnt signaling pathway and HPV infections 16, 18 and 45
are frequent events during multistage carcinogenesis, however, only a significant association
with SFRP2 methylation was observed. The methylation of gene promoter SOX17 was related
to lower cervical cancer severity but not to HPV types. Adenocarcinomas were significantlyassociated with HPV infections 16, 18 and 45, and demonstrated a borderline association with
DKK3 and SOX17 methylation. In summary, the results of the present study contribute to a
better understanding of carcinogenesis of the cervix in the Center-West of Brazil.
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SEGATI, K. D. Análise da metilação dos genes SOX17, DKK3 e SFRP2, tipos de HPV e associação com a origem e o estadiamento do câncer de colo uterino. 2017. 100 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2017.