Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma

Detalhes bibliográficos
Autor(a) principal: Canevari, Renata A.
Data de Publicação: 2016
Outros Autores: Marchi, Fabio A., Domingues, Maria A. C. [UNESP], de Andrade, Victor Piana, Caldeira, José R. F., Verjovski-Almeida, Sergio, Rogatto, Silvia R., Reis, Eduardo M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1007/s13277-016-5133-8
http://hdl.handle.net/11449/176939
Resumo: Breast carcinoma (BC) corresponds to 23 % of all cancers in women, with 1.38 million new cases and 460,000 deaths worldwide annually. Despite the significant advances in the identification of molecular markers and different modalities of treatment for primary BC, the ability to predict its metastatic behavior is still limited. The purpose of this study was to identify novel molecular markers associated with distinct clinical outcomes in a Brazilian cohort of BC patients. We generated global gene expression profiles using tumor samples from 24 patients with invasive ductal BC who were followed for at least 5 years, including a group of 15 patients with favorable outcomes and another with nine patients who developed metastasis. We identified a set of 58 differentially expressed genes (p ≤ 0.01) between the two groups. The prognostic value of this metastasis signature was corroborated by its ability to stratify independent BC patient datasets according to disease-free survival and overall survival. The upregulation of B3GNT7, PPM1D, TNKS2, PHB, and GTSE1 in patients with poor outcomes was confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in an independent sample of patients with BC (47 with good outcomes and eight that presented metastasis). The expression of BCL2-associated agonist of cell death (BAD) protein was determined in 1276 BC tissue samples by immunohistochemistry and was consistent with the reduced BAD mRNA expression levels in metastatic cases, as observed in the oligoarray data. These findings point to novel prognostic markers that can distinguish breast carcinomas with metastatic potential from those with favorable outcomes.
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spelling Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinomaBreast cancerGene expressionMetastasisPrognostic gene signatureTumor biomarkersBreast carcinoma (BC) corresponds to 23 % of all cancers in women, with 1.38 million new cases and 460,000 deaths worldwide annually. Despite the significant advances in the identification of molecular markers and different modalities of treatment for primary BC, the ability to predict its metastatic behavior is still limited. The purpose of this study was to identify novel molecular markers associated with distinct clinical outcomes in a Brazilian cohort of BC patients. We generated global gene expression profiles using tumor samples from 24 patients with invasive ductal BC who were followed for at least 5 years, including a group of 15 patients with favorable outcomes and another with nine patients who developed metastasis. We identified a set of 58 differentially expressed genes (p ≤ 0.01) between the two groups. The prognostic value of this metastasis signature was corroborated by its ability to stratify independent BC patient datasets according to disease-free survival and overall survival. The upregulation of B3GNT7, PPM1D, TNKS2, PHB, and GTSE1 in patients with poor outcomes was confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in an independent sample of patients with BC (47 with good outcomes and eight that presented metastasis). The expression of BCL2-associated agonist of cell death (BAD) protein was determined in 1276 BC tissue samples by immunohistochemistry and was consistent with the reduced BAD mRNA expression levels in metastatic cases, as observed in the oligoarray data. These findings point to novel prognostic markers that can distinguish breast carcinomas with metastatic potential from those with favorable outcomes.Instituto de Pesquisa e Desenvolvimento Universidade do Vale do ParaíbaCIPE - AC Camargo Cancer CenterDepartamento de Patologia Faculdade de Medicina Universidade do Estado de São Paulo - UNESPDepartamento de Patologia AC Camargo Cancer CenterDepartamento de Senologia Hospital Amaral CarvalhoDepartamento de Bioquímica Instituto de Química Universidade de São Paulo - USP, Av. Prof. Lineu Prestes, 748, Cidade UniversitariaInstituto ButantanDepartment of Clinical Genetics Vejle SygehusInstitute of Regional Health University of Southern DenmarkDepartamento de Patologia Faculdade de Medicina Universidade do Estado de São Paulo - UNESPUniversidade do Vale do ParaíbaCIPE - AC Camargo Cancer CenterUniversidade Estadual Paulista (Unesp)AC Camargo Cancer CenterHospital Amaral CarvalhoUniversidade de São Paulo (USP)Instituto ButantanUniversity of Southern DenmarkCanevari, Renata A.Marchi, Fabio A.Domingues, Maria A. C. [UNESP]de Andrade, Victor PianaCaldeira, José R. F.Verjovski-Almeida, SergioRogatto, Silvia R.Reis, Eduardo M.2018-12-11T17:23:11Z2018-12-11T17:23:11Z2016-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article13855-13870application/pdfhttp://dx.doi.org/10.1007/s13277-016-5133-8Tumor Biology, v. 37, n. 10, p. 13855-13870, 2016.1423-03801010-4283http://hdl.handle.net/11449/17693910.1007/s13277-016-5133-82-s2.0-849828100652-s2.0-84982810065.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengTumor Biology1,1491,149info:eu-repo/semantics/openAccess2024-01-05T06:22:14Zoai:repositorio.unesp.br:11449/176939Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:09:34.577194Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma
title Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma
spellingShingle Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma
Canevari, Renata A.
Breast cancer
Gene expression
Metastasis
Prognostic gene signature
Tumor biomarkers
title_short Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma
title_full Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma
title_fullStr Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma
title_full_unstemmed Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma
title_sort Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma
author Canevari, Renata A.
author_facet Canevari, Renata A.
Marchi, Fabio A.
Domingues, Maria A. C. [UNESP]
de Andrade, Victor Piana
Caldeira, José R. F.
Verjovski-Almeida, Sergio
Rogatto, Silvia R.
Reis, Eduardo M.
author_role author
author2 Marchi, Fabio A.
Domingues, Maria A. C. [UNESP]
de Andrade, Victor Piana
Caldeira, José R. F.
Verjovski-Almeida, Sergio
Rogatto, Silvia R.
Reis, Eduardo M.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Vale do Paraíba
CIPE - AC Camargo Cancer Center
Universidade Estadual Paulista (Unesp)
AC Camargo Cancer Center
Hospital Amaral Carvalho
Universidade de São Paulo (USP)
Instituto Butantan
University of Southern Denmark
dc.contributor.author.fl_str_mv Canevari, Renata A.
Marchi, Fabio A.
Domingues, Maria A. C. [UNESP]
de Andrade, Victor Piana
Caldeira, José R. F.
Verjovski-Almeida, Sergio
Rogatto, Silvia R.
Reis, Eduardo M.
dc.subject.por.fl_str_mv Breast cancer
Gene expression
Metastasis
Prognostic gene signature
Tumor biomarkers
topic Breast cancer
Gene expression
Metastasis
Prognostic gene signature
Tumor biomarkers
description Breast carcinoma (BC) corresponds to 23 % of all cancers in women, with 1.38 million new cases and 460,000 deaths worldwide annually. Despite the significant advances in the identification of molecular markers and different modalities of treatment for primary BC, the ability to predict its metastatic behavior is still limited. The purpose of this study was to identify novel molecular markers associated with distinct clinical outcomes in a Brazilian cohort of BC patients. We generated global gene expression profiles using tumor samples from 24 patients with invasive ductal BC who were followed for at least 5 years, including a group of 15 patients with favorable outcomes and another with nine patients who developed metastasis. We identified a set of 58 differentially expressed genes (p ≤ 0.01) between the two groups. The prognostic value of this metastasis signature was corroborated by its ability to stratify independent BC patient datasets according to disease-free survival and overall survival. The upregulation of B3GNT7, PPM1D, TNKS2, PHB, and GTSE1 in patients with poor outcomes was confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in an independent sample of patients with BC (47 with good outcomes and eight that presented metastasis). The expression of BCL2-associated agonist of cell death (BAD) protein was determined in 1276 BC tissue samples by immunohistochemistry and was consistent with the reduced BAD mRNA expression levels in metastatic cases, as observed in the oligoarray data. These findings point to novel prognostic markers that can distinguish breast carcinomas with metastatic potential from those with favorable outcomes.
publishDate 2016
dc.date.none.fl_str_mv 2016-10-01
2018-12-11T17:23:11Z
2018-12-11T17:23:11Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1007/s13277-016-5133-8
Tumor Biology, v. 37, n. 10, p. 13855-13870, 2016.
1423-0380
1010-4283
http://hdl.handle.net/11449/176939
10.1007/s13277-016-5133-8
2-s2.0-84982810065
2-s2.0-84982810065.pdf
url http://dx.doi.org/10.1007/s13277-016-5133-8
http://hdl.handle.net/11449/176939
identifier_str_mv Tumor Biology, v. 37, n. 10, p. 13855-13870, 2016.
1423-0380
1010-4283
10.1007/s13277-016-5133-8
2-s2.0-84982810065
2-s2.0-84982810065.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Tumor Biology
1,149
1,149
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13855-13870
application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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