Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral

Detalhes bibliográficos
Autor(a) principal: GOMES , Jhessica Ivanilde Silva
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFMA
Texto Completo: https://tedebc.ufma.br/jspui/handle/tede/tede/2882
Resumo: Penile cancer (PC) is considered rare cancer, with a higher incidence in men over 50 years. Human papillomavirus (HPV) is one of the risk factors for the development of this disease. In recent years, new therapeutic targets have been sought for various types of cancer, including the RANK / RANKL / OPG axis, as it remains unregulated in some tumors. This study aimed to evaluate the involvement of the RANK / RANKL / OPG axis in penile tumors and its association with tumor behavior. This is a cross-sectional quantitative study of 59 penile tumors stored in the Maranhão Tumor and DNA Biobank (BTMA). Sociodemographic data were obtained through a questionnaire; clinical and histopathological data were collected through medical record analysis. Genomic DNA was extracted and performed Nested PCR for HPV identification using the primers PGMY and GP, followed by agarose gel electrophoresis. Positive samples were submitted to sequencing sangers method for viral type identification. For the expression of RANK / RANKL / OPG axis, the following steps were performed: RNA extraction and quantification, RNA-cDNA conversion using reverse transcriptase enzyme and real-time quantitative polymerase chain reaction (qPCR). It was observed that the largest number of men were over 60 years old (63.0), income up to 1 minimum wage (51%), illiterate (42.0%) and residents of municipalities in the interior state of Maranhão (59 %) and had not performed circumcision (68%). Regarding the type of lesion, ulceration was predominant, representing 36% of cases. Regarding the histological subtype, the usual was the most prevalent (33,9%). According to the classification of PC by TNM staging (T-tumor size, N - lymph nodes, M - metastasis), 23,7% corresponded to stages II and III. There was a 73% prevalence of HPV, with subtypes 16 and 11 being the most found. In the analysis of gene expression of the RANK / RANKL / OPG axis, it was observed that, in the comparison of the medians between tumor and non-tumor tissues, there was no statistically significant association. When comparing the axis with clinical characteristics, there was no significance between these variables. The association of the axis and histopathology and lesion staging showed that RANK receptor expression was associated with the occurrence of perineural invasion and with the ulcerated lesion in tumor tissue. HPV subtypes were associated with the expression of RANK and RANKL. The profile of the patients were men over 60 years of age, with low education and residing in municipalities in the interior of the state of Maranhão. The high prevalence of HPV infection in the samples may be associated with low socioeconomic status and sexual habits. RANK receptor expression was associated with the occurrence of perineural invasion, a marker of tumor aggressiveness, which may also be associated with the presence of HPV. Further studies should be performed to investigate the role of the RANK, RANKL and OPG axis in penile carcinoma, preferably using other techniques such as immunohistochemistry.
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spelling BRITO, Luciane Maria Oliveirahttps://orcid.org/0000-0002-8574-9680http://lattes.cnpq.br/0446524487971854BRITO, Haissa Oliveirahttps://orcid.org/0000-0002-1189-8130http://lattes.cnpq.br/2303050934162020BRITO, Luciane Maria Oliveirahttps://orcid.org/0000-0002-8574-9680http://lattes.cnpq.br/0446524487971854BRITO, Haissa Oliveirahttps://orcid.org/0000-0002-1189-8130http://lattes.cnpq.br/2303050934162020AVILA, Elda Pereira Noronhahttp://lattes.cnpq.br/9711847705518162OLIVEIRA, Rui Miguel Gil da Costahttps://orcid.org/0000-0002-2151-2449http://lattes.cnpq.br/6785759461393904SILVA, Marcelo Magalhães604140153-63http://lattes.cnpq.br/0613005185336485GOMES , Jhessica Ivanilde Silva2019-10-10T20:06:22Z2019-09-13GOMES, Jhessica Ivanilde Silva. Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral. 2019. 100f. Dissertação (Programa de Pós-Graduação em Saúde do Adulto e da Criança/CCBS) - Universidade Federal do Maranhão, São Luís.https://tedebc.ufma.br/jspui/handle/tede/tede/2882Penile cancer (PC) is considered rare cancer, with a higher incidence in men over 50 years. Human papillomavirus (HPV) is one of the risk factors for the development of this disease. In recent years, new therapeutic targets have been sought for various types of cancer, including the RANK / RANKL / OPG axis, as it remains unregulated in some tumors. This study aimed to evaluate the involvement of the RANK / RANKL / OPG axis in penile tumors and its association with tumor behavior. This is a cross-sectional quantitative study of 59 penile tumors stored in the Maranhão Tumor and DNA Biobank (BTMA). Sociodemographic data were obtained through a questionnaire; clinical and histopathological data were collected through medical record analysis. Genomic DNA was extracted and performed Nested PCR for HPV identification using the primers PGMY and GP, followed by agarose gel electrophoresis. Positive samples were submitted to sequencing sangers method for viral type identification. For the expression of RANK / RANKL / OPG axis, the following steps were performed: RNA extraction and quantification, RNA-cDNA conversion using reverse transcriptase enzyme and real-time quantitative polymerase chain reaction (qPCR). It was observed that the largest number of men were over 60 years old (63.0), income up to 1 minimum wage (51%), illiterate (42.0%) and residents of municipalities in the interior state of Maranhão (59 %) and had not performed circumcision (68%). Regarding the type of lesion, ulceration was predominant, representing 36% of cases. Regarding the histological subtype, the usual was the most prevalent (33,9%). According to the classification of PC by TNM staging (T-tumor size, N - lymph nodes, M - metastasis), 23,7% corresponded to stages II and III. There was a 73% prevalence of HPV, with subtypes 16 and 11 being the most found. In the analysis of gene expression of the RANK / RANKL / OPG axis, it was observed that, in the comparison of the medians between tumor and non-tumor tissues, there was no statistically significant association. When comparing the axis with clinical characteristics, there was no significance between these variables. The association of the axis and histopathology and lesion staging showed that RANK receptor expression was associated with the occurrence of perineural invasion and with the ulcerated lesion in tumor tissue. HPV subtypes were associated with the expression of RANK and RANKL. The profile of the patients were men over 60 years of age, with low education and residing in municipalities in the interior of the state of Maranhão. The high prevalence of HPV infection in the samples may be associated with low socioeconomic status and sexual habits. RANK receptor expression was associated with the occurrence of perineural invasion, a marker of tumor aggressiveness, which may also be associated with the presence of HPV. Further studies should be performed to investigate the role of the RANK, RANKL and OPG axis in penile carcinoma, preferably using other techniques such as immunohistochemistry.O câncer de pênis (CP) é considerado uma neoplasia rara, com maior incidência em homens com idade superior a 50 anos. O Papilomavírus Humano (HPV) é um dos fatores de risco para o desenvolvimento desta doença. Nos últimos anos tem se buscado novos alvos terapêuticos para diversos tipos de câncer, entre eles o eixo RANK/RANKL/OPG, pois o mesmo permanece desregulado em alguns tumores. O objetivo geral deste trabalho foi avaliar o envolvimento do eixo RANK/RANKL/OPG em tumores penianos e sua associação com o comportamento tumoral. Trata-se de um estudo quantitativo transversal com 59 amostras de tumores penianos armazenados no Biobanco de Tumores e DNA do Maranhão (BTMA). Dados sóciodemográficos foram obtidos através de um questionário, dados clínicos e histopatológicos foram coletados por meio de análise de prontuário. O DNA genômico das amostras foi extraído e realizado a PCR/Nested para identificação do HPV utilizando os primers PGMY e GP+ e em seguida a eletroferese em gel de agarose. Amostras positivas foram submetidas ao sequenciamento pelo método de Sangers para identificção do tipo viral. Para a expressão gênica do eixo RANK/RANKL/OPG foi realizado as etapas: extração e quantificação de RNA, conversão de RNA em cDNA através da enzima trancriptase reversa e reação em cadeia de polimerase quantitativa em tempo real (qPCR). Observou-se que o maior quantitativo de homens tinha idade superior a 60 anos (63,0), renda de até 1 salário mínimo (51%), analfabetos (42,0%), residentes em municípios do interior estado do Maranhão (59%) e não haviam realizado circuncisão (68%). Quanto ao tipo de lesão, a ulcerada foi a mais predominante, representando 36% dos casos. Em relação ao subtipo histológico, o usual foi o mais prevalente (33.9%). Conforme a classificação do CP através do estadiamento TNM (T- tamanho do tumor, N – linfonodos, M – Metástase) 23,7% correspondiam aos estádios II e III. Houve uma prevalência de 73% de HPV nas amostras, sendo os subtipos 16 e 11 os mais encontrados. Na análise da expressão gênica do eixo RANK/RANKL/OPG observou-se que na comparação das medianas entre tecidos tumorais e não tumorais não houve associação estatisticamente significante. Quando comparou-se o eixo com características clínicas não existiu nenhuma significância com as variáveis analisadas. A associação do eixo com a histopatologia e o estadiamento da lesão mostrou que a expressão do receptor RANK esteve associada com a ocorrência de invasão perineural e com lesão ulcerada em tecido tumoral. Na comparação do sistema com o HPV, houve corrrelação dos subtipos de HPV com a expressão de RANK e RANKL. O perfil dos pacientes foram homens acima de 60 anos de idade, de baixa escolaridade e que residiam em municípios do interior do estado do Maranhão. A alta prevalência de infecção por HPV nas amostras pode estar associado ao baixo nível socioeconômico e hábitos sexuais. A expressão do receptor RANK esteve associada com a ocorrência de invasão perineural um marcador de agressividade tumoral, o qual pode estar associado também com a presença de HPV. Maiores estudos devem ser realizados investigando o papel do eixo RANK, RANKL e OPG no carcinoma peniano, preferencialmente, utilizando outras técnicas como imunohistoquímica.Submitted by Sheila MONTEIRO (sheila.monteiro@ufma.br) on 2019-10-10T20:06:22Z No. of bitstreams: 1 JHESSICA-GOMES.pdf: 2012509 bytes, checksum: 676a877e4d6b0ad0c428820e3a8c580f (MD5)Made available in DSpace on 2019-10-10T20:06:22Z (GMT). No. of bitstreams: 1 JHESSICA-GOMES.pdf: 2012509 bytes, checksum: 676a877e4d6b0ad0c428820e3a8c580f (MD5) Previous issue date: 2019-09-13Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESFundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão - FAPEMAapplication/pdfporUniversidade Federal do MaranhãoPROGRAMA DE PÓS-GRADUAÇÃO EM SAÚDE DO ADULTO E DA CRIANÇA/CCBSUFMABrasilDEPARTAMENTO DE MEDICINA III/CCBSCâncer de pênisHPVRANKRANKLOPGPenile cancerHPVRANKRANKLOPGCiências da SaúdeCancerologiaEnvolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoralRank / Rankl / OPG axis involvement in penile tumors and its association with tumor behaviorinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFMAinstname:Universidade Federal do Maranhão (UFMA)instacron:UFMAORIGINALJHESSICA-GOMES.pdfJHESSICA-GOMES.pdfapplication/pdf2012509http://tedebc.ufma.br:8080/bitstream/tede/2882/2/JHESSICA-GOMES.pdf676a877e4d6b0ad0c428820e3a8c580fMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82255http://tedebc.ufma.br:8080/bitstream/tede/2882/1/license.txt97eeade1fce43278e63fe063657f8083MD51tede/28822019-10-10 17:06:22.518oai:tede2:tede/2882Biblioteca Digital de Teses e Dissertaçõeshttps://tedebc.ufma.br/jspui/PUBhttp://tedebc.ufma.br:8080/oai/requestrepositorio@ufma.br||repositorio@ufma.bropendoar:21312019-10-10T20:06:22Biblioteca Digital de Teses e Dissertações da UFMA - Universidade Federal do Maranhão (UFMA)false
dc.title.por.fl_str_mv Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral
dc.title.alternative.eng.fl_str_mv Rank / Rankl / OPG axis involvement in penile tumors and its association with tumor behavior
title Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral
spellingShingle Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral
GOMES , Jhessica Ivanilde Silva
Câncer de pênis
HPV
RANK
RANKL
OPG
Penile cancer
HPV
RANK
RANKL
OPG
Ciências da Saúde
Cancerologia
title_short Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral
title_full Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral
title_fullStr Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral
title_full_unstemmed Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral
title_sort Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral
author GOMES , Jhessica Ivanilde Silva
author_facet GOMES , Jhessica Ivanilde Silva
author_role author
dc.contributor.advisor1.fl_str_mv BRITO, Luciane Maria Oliveira
dc.contributor.advisor1ID.fl_str_mv https://orcid.org/0000-0002-8574-9680
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/0446524487971854
dc.contributor.advisor-co1.fl_str_mv BRITO, Haissa Oliveira
dc.contributor.advisor-co1ID.fl_str_mv https://orcid.org/0000-0002-1189-8130
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/2303050934162020
dc.contributor.referee1.fl_str_mv BRITO, Luciane Maria Oliveira
dc.contributor.referee1ID.fl_str_mv https://orcid.org/0000-0002-8574-9680
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/0446524487971854
dc.contributor.referee2.fl_str_mv BRITO, Haissa Oliveira
dc.contributor.referee2ID.fl_str_mv https://orcid.org/0000-0002-1189-8130
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/2303050934162020
dc.contributor.referee3.fl_str_mv AVILA, Elda Pereira Noronha
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/9711847705518162
dc.contributor.referee4.fl_str_mv OLIVEIRA, Rui Miguel Gil da Costa
dc.contributor.referee4ID.fl_str_mv https://orcid.org/0000-0002-2151-2449
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/6785759461393904
dc.contributor.referee5.fl_str_mv SILVA, Marcelo Magalhães
dc.contributor.authorID.fl_str_mv 604140153-63
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/0613005185336485
dc.contributor.author.fl_str_mv GOMES , Jhessica Ivanilde Silva
contributor_str_mv BRITO, Luciane Maria Oliveira
BRITO, Haissa Oliveira
BRITO, Luciane Maria Oliveira
BRITO, Haissa Oliveira
AVILA, Elda Pereira Noronha
OLIVEIRA, Rui Miguel Gil da Costa
SILVA, Marcelo Magalhães
dc.subject.por.fl_str_mv Câncer de pênis
HPV
RANK
RANKL
OPG
topic Câncer de pênis
HPV
RANK
RANKL
OPG
Penile cancer
HPV
RANK
RANKL
OPG
Ciências da Saúde
Cancerologia
dc.subject.eng.fl_str_mv Penile cancer
HPV
RANK
RANKL
OPG
dc.subject.cnpq.fl_str_mv Ciências da Saúde
Cancerologia
description Penile cancer (PC) is considered rare cancer, with a higher incidence in men over 50 years. Human papillomavirus (HPV) is one of the risk factors for the development of this disease. In recent years, new therapeutic targets have been sought for various types of cancer, including the RANK / RANKL / OPG axis, as it remains unregulated in some tumors. This study aimed to evaluate the involvement of the RANK / RANKL / OPG axis in penile tumors and its association with tumor behavior. This is a cross-sectional quantitative study of 59 penile tumors stored in the Maranhão Tumor and DNA Biobank (BTMA). Sociodemographic data were obtained through a questionnaire; clinical and histopathological data were collected through medical record analysis. Genomic DNA was extracted and performed Nested PCR for HPV identification using the primers PGMY and GP, followed by agarose gel electrophoresis. Positive samples were submitted to sequencing sangers method for viral type identification. For the expression of RANK / RANKL / OPG axis, the following steps were performed: RNA extraction and quantification, RNA-cDNA conversion using reverse transcriptase enzyme and real-time quantitative polymerase chain reaction (qPCR). It was observed that the largest number of men were over 60 years old (63.0), income up to 1 minimum wage (51%), illiterate (42.0%) and residents of municipalities in the interior state of Maranhão (59 %) and had not performed circumcision (68%). Regarding the type of lesion, ulceration was predominant, representing 36% of cases. Regarding the histological subtype, the usual was the most prevalent (33,9%). According to the classification of PC by TNM staging (T-tumor size, N - lymph nodes, M - metastasis), 23,7% corresponded to stages II and III. There was a 73% prevalence of HPV, with subtypes 16 and 11 being the most found. In the analysis of gene expression of the RANK / RANKL / OPG axis, it was observed that, in the comparison of the medians between tumor and non-tumor tissues, there was no statistically significant association. When comparing the axis with clinical characteristics, there was no significance between these variables. The association of the axis and histopathology and lesion staging showed that RANK receptor expression was associated with the occurrence of perineural invasion and with the ulcerated lesion in tumor tissue. HPV subtypes were associated with the expression of RANK and RANKL. The profile of the patients were men over 60 years of age, with low education and residing in municipalities in the interior of the state of Maranhão. The high prevalence of HPV infection in the samples may be associated with low socioeconomic status and sexual habits. RANK receptor expression was associated with the occurrence of perineural invasion, a marker of tumor aggressiveness, which may also be associated with the presence of HPV. Further studies should be performed to investigate the role of the RANK, RANKL and OPG axis in penile carcinoma, preferably using other techniques such as immunohistochemistry.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-10-10T20:06:22Z
dc.date.issued.fl_str_mv 2019-09-13
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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status_str publishedVersion
dc.identifier.citation.fl_str_mv GOMES, Jhessica Ivanilde Silva. Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral. 2019. 100f. Dissertação (Programa de Pós-Graduação em Saúde do Adulto e da Criança/CCBS) - Universidade Federal do Maranhão, São Luís.
dc.identifier.uri.fl_str_mv https://tedebc.ufma.br/jspui/handle/tede/tede/2882
identifier_str_mv GOMES, Jhessica Ivanilde Silva. Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral. 2019. 100f. Dissertação (Programa de Pós-Graduação em Saúde do Adulto e da Criança/CCBS) - Universidade Federal do Maranhão, São Luís.
url https://tedebc.ufma.br/jspui/handle/tede/tede/2882
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dc.publisher.none.fl_str_mv Universidade Federal do Maranhão
dc.publisher.program.fl_str_mv PROGRAMA DE PÓS-GRADUAÇÃO EM SAÚDE DO ADULTO E DA CRIANÇA/CCBS
dc.publisher.initials.fl_str_mv UFMA
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv DEPARTAMENTO DE MEDICINA III/CCBS
publisher.none.fl_str_mv Universidade Federal do Maranhão
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