Avaliação do receptor purinérgico P2X7 e da CD73 como biomarcadores em pacientes idosas com câncer de mama
Autor(a) principal: | |
---|---|
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. |
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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 |
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2022-07-06T13:28:49Z |
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2022-03-28 |
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