Avaliação do receptor purinérgico P2X7 e da CD73 como biomarcadores em pacientes idosas com câncer de mama

Detalhes bibliográficos
Autor(a) principal: Silva, Jéssica Gollmann da
Data de Publicação: 2022
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da PUC_RS
Texto Completo: https://tede2.pucrs.br/tede2/handle/tede/10341
Resumo: Breast cancer is the most prevalent neoplasm in women worldwide. Elderly women are frequently excluded from clinical studies, with a deficit in the collection of prospective data for this age group and, consequently, they are evaluated and treated according to the studies and guidelines evaluated in young women. In recent years, the focus for new types of breast cancer diagnosis and treatment has been on purinergic signaling and its role in tumor promotion and progression. The tumor microenvironment is rich in ATP production and release, which after a series of steps acts on the P2X and P2Y purinergic receptors, mediating various biological functions in the tumor, such as cell proliferation, migration, differentiation, and cell death. Therefore, the aim of this study was to evaluate the expression of the ionotropic receptor P2X7 and CD73 in biopsies of elderly patients with breast cancer and to relate them as possible prognostic biomarkers and/or therapeutic targets, in order to improve disease outcomes in this group of patients. Samples were collected from 22 elderly patients (> 60 years), assisted by the Unified Health System at the Oncology Service of Hospital São Lucas da PUCRS at the time of diagnosis, and from 12 elderly patients without a diagnosis of cancer (control group). The most expressive cancer subtype in the sample was HER2+ in 7 women (31.8%), followed by luminal B (27.3%), luminal A (22.7%) and triple negative (18.2%). The TNM system was used to classify cancer staging, where 15 elderly women (68.2%) had Clinical Stage I and II and 7 (31.8%) had Clinical Stage III and IV, representing the highest level of severity. of the disease. The evaluation of P2X7 and CD73 expression was performed using the immunohistochemical technique and was analyzed by a professional pathologist. Regarding P2X7, women aged 60 to 69 years and ≥ 70 years represented the highest number in the mildly expressed tumor grade (grade 1) 53.3% and 57.1% respectively. In the CD73 analysis, women aged 60 to 69 years maintained the representation of the highest number in the mildly expressed tumor grade (60%), but women aged ≥ 70 years had a higher incidence in the highly expressed category (grade 3), with 42, 8% of them. The expression of markers in the blood of elderly patients with breast cancer was also evaluated and compared with control patients, but there was no statistically significant difference. Data extracted from the TCGA showed that elderly women with stage T2 breast cancer had higher expression of CD73. Therefore, the need for research on the purinergic system, particularly the P2X7 and CD73 proteins, and breast cancer in elderly women is evident.
id P_RS_fe5c4879fe63815e6978d1341f5436d8
oai_identifier_str oai:tede2.pucrs.br:tede/10341
network_acronym_str P_RS
network_name_str Biblioteca Digital de Teses e Dissertações da PUC_RS
repository_id_str
spelling Morrone, Fernanda Buenohttp://lattes.cnpq.br/8543061247854357http://lattes.cnpq.br/8057299513287396Silva, Jéssica Gollmann da2022-07-06T13:28:49Z2022-03-28https://tede2.pucrs.br/tede2/handle/tede/10341Breast cancer is the most prevalent neoplasm in women worldwide. Elderly women are frequently excluded from clinical studies, with a deficit in the collection of prospective data for this age group and, consequently, they are evaluated and treated according to the studies and guidelines evaluated in young women. In recent years, the focus for new types of breast cancer diagnosis and treatment has been on purinergic signaling and its role in tumor promotion and progression. The tumor microenvironment is rich in ATP production and release, which after a series of steps acts on the P2X and P2Y purinergic receptors, mediating various biological functions in the tumor, such as cell proliferation, migration, differentiation, and cell death. Therefore, the aim of this study was to evaluate the expression of the ionotropic receptor P2X7 and CD73 in biopsies of elderly patients with breast cancer and to relate them as possible prognostic biomarkers and/or therapeutic targets, in order to improve disease outcomes in this group of patients. Samples were collected from 22 elderly patients (> 60 years), assisted by the Unified Health System at the Oncology Service of Hospital São Lucas da PUCRS at the time of diagnosis, and from 12 elderly patients without a diagnosis of cancer (control group). The most expressive cancer subtype in the sample was HER2+ in 7 women (31.8%), followed by luminal B (27.3%), luminal A (22.7%) and triple negative (18.2%). The TNM system was used to classify cancer staging, where 15 elderly women (68.2%) had Clinical Stage I and II and 7 (31.8%) had Clinical Stage III and IV, representing the highest level of severity. of the disease. The evaluation of P2X7 and CD73 expression was performed using the immunohistochemical technique and was analyzed by a professional pathologist. Regarding P2X7, women aged 60 to 69 years and ≥ 70 years represented the highest number in the mildly expressed tumor grade (grade 1) 53.3% and 57.1% respectively. In the CD73 analysis, women aged 60 to 69 years maintained the representation of the highest number in the mildly expressed tumor grade (60%), but women aged ≥ 70 years had a higher incidence in the highly expressed category (grade 3), with 42, 8% of them. The expression of markers in the blood of elderly patients with breast cancer was also evaluated and compared with control patients, but there was no statistically significant difference. Data extracted from the TCGA showed that elderly women with stage T2 breast cancer had higher expression of CD73. Therefore, the need for research on the purinergic system, particularly the P2X7 and CD73 proteins, and breast cancer in elderly women is evident.O câncer de mama é a neoplasia mais prevalente nas mulheres em todo o mundo. As mulheres idosas são frequentemente excluídas de estudos clínicos, ocorrendo déficit de coleta de dados prospectivos desta faixa etária e, consequentemente, são avaliadas e tratadas conforme os estudos e diretrizes avaliados em mulheres jovens. Nos últimos anos o foco para novos tipos de diagnóstico e tratamento do câncer de mama tem se voltado à sinalização purinérgica e seu papel na promoção e progressão tumoral. O microambiente tumoral é rico em produção e liberação de ATP, que após uma série de etapas atua nos receptores purinérgicos P2X e P2Y, mediando várias funções biológicas no tumor, como proliferação celular, migração, diferenciação e morte celular. Portanto, o objetivo desde estudo foi avaliar a expressão do receptor ionotrópico P2X7 e da CD73 em biópsias de pacientes idosas com câncer de mama e relacionar como possíveis biomarcadores prognósticos e/ou alvos terapêuticos, a fim de aprimorar os desfechos da doença nesse grupo de pacientes. Foram coletadas amostras de 22 pacientes idosas (> 60 anos), atendidas pelo Sistema Único de Saúde no Serviço de Oncologia do Hospital São Lucas da PUCRS no momento do diagnóstico, e de 12 pacientes idosas sem diagnóstico de câncer (grupo controle). O subtipo de câncer mais expressivo na amostra foi o HER2+ em 7 mulheres (31,8%), seguidos de luminal B (27,3%), luminal A (22,7%) e triplo negativo (18,2%). Foi utilizado o sistema TNM para classificar o estadiamento do câncer, onde 15 idosas (68,2%) apresentaram o Estágio Clínico I e II e 7 (31,8%) apresentaram o Estágio Clínico III e IV, representando o maior nível de severidade da doença. A avaliação da expressão de P2X7 e CD73 foi realizada através da técnica de imunohistoquímica e foi analisada por uma profissional patologista. Em relação ao P2X7, as mulheres com idade de 60 a 69 anos e ≥ 70 anos representaram o maior número no grau tumoral levemente expresso (grau 1) 53,3% e 57,1% respectivamente. Na análise da CD73, as mulheres com 60 a 69 anos mantiveram a representação do maior número no grau tumoral levemente expresso (60%), porém as mulheres com ≥ 70 anos tiveram maior incidência na categoria altamente expresso (grau 3), com 42,8% delas. Também foi avaliada a expressão dos marcadores no sangue das pacientes idosas com câncer de mama e comparado com pacientes controle, porém não houve diferença estatística significativa. Os dados extraídos do TCGA demonstraram que as mulheres idosas com câncer de mama em estágio T2 apresentaram maior expressão de CD73. Portanto, fica evidente a necessidade das pesquisas sobre o sistema purinérgico, particularmente as proteínas P2X7 e CD73, e o câncer de mama em mulheres idosas.Submitted by PPG Medicina e Ciências da Saúde (medicina-pg@pucrs.br) on 2022-06-24T19:16:54Z No. of bitstreams: 1 Jessica-Gollmann-da-Silva-PPG-Medicina-Dissertação-de-mestrado-pós-banca2 (3).pdf: 3581720 bytes, checksum: df3914eb374d52183cff4c2ad2dcd394 (MD5)Rejected by Sheila Dias (sheila.dias@pucrs.br), reason: Devolvido devido ao trabalho ter vindo com divergência entre títulos. on 2022-06-27T19:33:30Z (GMT)Submitted by PPG Medicina e Ciências da Saúde (medicina-pg@pucrs.br) on 2022-07-06T12:35:56Z No. of bitstreams: 1 Jessica-Gollmann-da-Silva-PPG-Medicina-Dissertação-de-mestrado-pós-banca2 (3).pdf: 3210128 bytes, checksum: b73337fddd5d0497cc9986fc92ee0670 (MD5)Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2022-07-06T13:15:32Z (GMT) No. of bitstreams: 1 Jessica-Gollmann-da-Silva-PPG-Medicina-Dissertação-de-mestrado-pós-banca2 (3).pdf: 3210128 bytes, checksum: b73337fddd5d0497cc9986fc92ee0670 (MD5)Made available in DSpace on 2022-07-06T13:28:49Z (GMT). No. of bitstreams: 1 Jessica-Gollmann-da-Silva-PPG-Medicina-Dissertação-de-mestrado-pós-banca2 (3).pdf: 3210128 bytes, checksum: b73337fddd5d0497cc9986fc92ee0670 (MD5) Previous issue date: 2022-03-28Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfhttps://tede2.pucrs.br/tede2/retrieve/184712/DIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdf.jpgporPontifícia Universidade Católica do Rio Grande do SulPrograma de Pós-Graduação em Medicina e Ciências da SaúdePUCRSBrasilEscola de MedicinaCâncer de MamaMulheres IdosasP2X7CD73Sistema PurinérgicoBreast CancerElderly WomenPurinergic SystemCIENCIAS DA SAUDE::MEDICINAAvaliação do receptor purinérgico P2X7 e da CD73 como biomarcadores em pacientes idosas com câncer de mamainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisTrabalho será publicado como artigo ou livro60 meses06/07/2027-721401722658532398500500500600-224747486637135387-9693694523087866273590462550136975366info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAILDIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdf.jpgDIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdf.jpgimage/jpeg4132https://tede2.pucrs.br/tede2/bitstream/tede/10341/6/DIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdf.jpg91cdc605bb13e1c765d1a457155ec6c8MD56TEXTDIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdf.txtDIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdf.txttext/plain1368https://tede2.pucrs.br/tede2/bitstream/tede/10341/5/DIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdf.txtb48d94b3aaf84249be7f875149afc034MD55ORIGINALDIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdfDIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdfapplication/pdf749724https://tede2.pucrs.br/tede2/bitstream/tede/10341/4/DIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdf6e126a114cdbedcb0db979ddb00e66d5MD54LICENSElicense.txtlicense.txttext/plain; charset=utf-8590https://tede2.pucrs.br/tede2/bitstream/tede/10341/3/license.txt220e11f2d3ba5354f917c7035aadef24MD53tede/103412022-07-06 12:00:16.072oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2022-07-06T15:00:16Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false
dc.title.por.fl_str_mv Avaliação do receptor purinérgico P2X7 e da CD73 como biomarcadores em pacientes idosas com câncer de mama
title Avaliação do receptor purinérgico P2X7 e da CD73 como biomarcadores em pacientes idosas com câncer de mama
spellingShingle Avaliação do receptor purinérgico P2X7 e da CD73 como biomarcadores em pacientes idosas com câncer de mama
Silva, Jéssica Gollmann da
Câncer de Mama
Mulheres Idosas
P2X7
CD73
Sistema Purinérgico
Breast Cancer
Elderly Women
Purinergic System
CIENCIAS DA SAUDE::MEDICINA
title_short Avaliação do receptor purinérgico P2X7 e da CD73 como biomarcadores em pacientes idosas com câncer de mama
title_full Avaliação do receptor purinérgico P2X7 e da CD73 como biomarcadores em pacientes idosas com câncer de mama
title_fullStr Avaliação do receptor purinérgico P2X7 e da CD73 como biomarcadores em pacientes idosas com câncer de mama
title_full_unstemmed Avaliação do receptor purinérgico P2X7 e da CD73 como biomarcadores em pacientes idosas com câncer de mama
title_sort Avaliação do receptor purinérgico P2X7 e da CD73 como biomarcadores em pacientes idosas com câncer de mama
author Silva, Jéssica Gollmann da
author_facet Silva, Jéssica Gollmann da
author_role author
dc.contributor.advisor1.fl_str_mv Morrone, Fernanda Bueno
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/8543061247854357
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/8057299513287396
dc.contributor.author.fl_str_mv Silva, Jéssica Gollmann da
contributor_str_mv Morrone, Fernanda Bueno
dc.subject.por.fl_str_mv Câncer de Mama
Mulheres Idosas
P2X7
CD73
Sistema Purinérgico
topic Câncer de Mama
Mulheres Idosas
P2X7
CD73
Sistema Purinérgico
Breast Cancer
Elderly Women
Purinergic System
CIENCIAS DA SAUDE::MEDICINA
dc.subject.eng.fl_str_mv Breast Cancer
Elderly Women
Purinergic System
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::MEDICINA
description Breast cancer is the most prevalent neoplasm in women worldwide. Elderly women are frequently excluded from clinical studies, with a deficit in the collection of prospective data for this age group and, consequently, they are evaluated and treated according to the studies and guidelines evaluated in young women. In recent years, the focus for new types of breast cancer diagnosis and treatment has been on purinergic signaling and its role in tumor promotion and progression. The tumor microenvironment is rich in ATP production and release, which after a series of steps acts on the P2X and P2Y purinergic receptors, mediating various biological functions in the tumor, such as cell proliferation, migration, differentiation, and cell death. Therefore, the aim of this study was to evaluate the expression of the ionotropic receptor P2X7 and CD73 in biopsies of elderly patients with breast cancer and to relate them as possible prognostic biomarkers and/or therapeutic targets, in order to improve disease outcomes in this group of patients. Samples were collected from 22 elderly patients (> 60 years), assisted by the Unified Health System at the Oncology Service of Hospital São Lucas da PUCRS at the time of diagnosis, and from 12 elderly patients without a diagnosis of cancer (control group). The most expressive cancer subtype in the sample was HER2+ in 7 women (31.8%), followed by luminal B (27.3%), luminal A (22.7%) and triple negative (18.2%). The TNM system was used to classify cancer staging, where 15 elderly women (68.2%) had Clinical Stage I and II and 7 (31.8%) had Clinical Stage III and IV, representing the highest level of severity. of the disease. The evaluation of P2X7 and CD73 expression was performed using the immunohistochemical technique and was analyzed by a professional pathologist. Regarding P2X7, women aged 60 to 69 years and ≥ 70 years represented the highest number in the mildly expressed tumor grade (grade 1) 53.3% and 57.1% respectively. In the CD73 analysis, women aged 60 to 69 years maintained the representation of the highest number in the mildly expressed tumor grade (60%), but women aged ≥ 70 years had a higher incidence in the highly expressed category (grade 3), with 42, 8% of them. The expression of markers in the blood of elderly patients with breast cancer was also evaluated and compared with control patients, but there was no statistically significant difference. Data extracted from the TCGA showed that elderly women with stage T2 breast cancer had higher expression of CD73. Therefore, the need for research on the purinergic system, particularly the P2X7 and CD73 proteins, and breast cancer in elderly women is evident.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-07-06T13:28:49Z
dc.date.issued.fl_str_mv 2022-03-28
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 https://tede2.pucrs.br/tede2/handle/tede/10341
url https://tede2.pucrs.br/tede2/handle/tede/10341
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv -721401722658532398
dc.relation.confidence.fl_str_mv 500
500
500
600
dc.relation.department.fl_str_mv -224747486637135387
dc.relation.cnpq.fl_str_mv -969369452308786627
dc.relation.sponsorship.fl_str_mv 3590462550136975366
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Pontifícia Universidade Católica do Rio Grande do Sul
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Medicina e Ciências da Saúde
dc.publisher.initials.fl_str_mv PUCRS
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Escola de Medicina
publisher.none.fl_str_mv Pontifícia Universidade Católica do Rio Grande do Sul
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS
instname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
instacron:PUC_RS
instname_str Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
instacron_str PUC_RS
institution PUC_RS
reponame_str Biblioteca Digital de Teses e Dissertações da PUC_RS
collection Biblioteca Digital de Teses e Dissertações da PUC_RS
bitstream.url.fl_str_mv https://tede2.pucrs.br/tede2/bitstream/tede/10341/6/DIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdf.jpg
https://tede2.pucrs.br/tede2/bitstream/tede/10341/5/DIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdf.txt
https://tede2.pucrs.br/tede2/bitstream/tede/10341/4/DIS_JESSICA_GOLLMANN_DA_SILVA_CONFIDENCIAL.pdf
https://tede2.pucrs.br/tede2/bitstream/tede/10341/3/license.txt
bitstream.checksum.fl_str_mv 91cdc605bb13e1c765d1a457155ec6c8
b48d94b3aaf84249be7f875149afc034
6e126a114cdbedcb0db979ddb00e66d5
220e11f2d3ba5354f917c7035aadef24
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
repository.mail.fl_str_mv biblioteca.central@pucrs.br||
_version_ 1799765356542164992