Minichromosome maintenance protein (MCM)-7 e a sua correlação com o papilomavírus humano na patogênese do câncer do colo do útero

• Ano de defesa: 2021
• Autor(a) principal: Larissa Rodrigues Peixoto
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - DEPARTAMENTO DE MORFOLOGIA; ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS; Programa de Pós-Graduação em Biologia Celular; UFMG
• Palavras-chave em Português: MCM7; Câncer do colo do útero; HPV; Imuno-histoquímica; Genotipagem; Biomarcadores de prognóstico; Componente 7 do complexo de manutenção de minicromossomo; Neoplasias do colo do útero; Papillomaviridae; Técnicas de genotipagem; Biomarcadores
• Link de acesso: http://hdl.handle.net/1843/35231

Cervical cancer (CC) affects more than 500,000 women by year worldwide, and it is considered one of the most important causes of cancer-related deaths in the female population. In the last two decades, the interest for the development of biomarkers that can identify cellular changes resulting from viral transformation has considerably grown. The employment of these cell markers may improve the sensitivity and the specificity of CC screening, diagnosis, and prognosis methods. The Minichromosome maintenance (MCMs) proteins, including MCM7 are essential for DNA replication and cell cycle control and, therefore, they are used in many studies as proliferation and prognostic biomarkers in different types of carcinomas. Our hypothesis is that the protein MCM7 has potency to be evaluated as a prognostic biomarker for the CC, from whose immuno-staining in cervical tissues would be related to the presence of high-risk (HR) Human Papillomavirus (HR-HPVs). Therefore, in this study, 43 cervical cancer tissues and 15 cervicitis (control) samples obtained by biopsy were evaluated concerning the tissue immune labeling for MCM7 by using immunohistochemistry (IHC) and a morphometric-based analysis of the labeled area. In addition, presence of DNA-HPV and DNA-HPV16 was also analyzed using DNA samples extracted from cervical tissues, and by means of Nested-PCR and Hemi-nested PCR protocols, respectively. Presence of DNA-HPV was observed in most of cervical tissue samples, and approximately half of samples were positive for DNA-HPV16. Regarding the MCM7 expression in cervical tissues, a nuclear protein staining was observed in cells from the basal and parabasal layers of the normal epithelium in cervicitis samples. Strong nuclear labeling of MCM7 was mainly found in tumor cells from epithelial origin in tumor nests located in the connective tissue. However, diffuse areas of unlabeled cells were noted in tumors nests composed by more atypical cells and exhibiting a higher differentiation degree. Regarding the cell density (cellularity) parameter, CC samples showed higher number of MCM7-labeled cell, when compared with tissues from the cervicitis group. It was found that the cancer groups diagnosed as poorly (CCEP) and moderately (CCEM) differentiated showed a correlation between the number of MCM7-positive cells, and the total number of cells counted in the complete injured areas. In addition, a correlation between the total number of cells labeled for MCM7 in CCEP and in CCEM, and the complete cancer area was observed. Concerning the differentiation tumor grading, CCEP is a tumor with higher proliferation rates and aggressive behavior than CCEM cancers. Regarding the presence of HPV and HPV16 DNA, it was found that the number of CCEP samples which presented a higher number of MCM7-positive cells and positivity for HPV16- DNA, were greater when compared to cancer samples from the CCEM group exhibiting similar aspects. Therefore, our study points to the potential use of MCM7 as a biomarker of the severity of this HPV-associated cancer that may significantly improve the diagnosis, and assist the monitoring of women with CC.