Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race

Autores
Singhal, Sandeep K.; Byun, Jung S.; Yan, Tingfen; Yancey, Ryan; Caban, Ambar; Hernandez, Sara Gil; Bufford, Sediqua; Hewitt, Stephen M.; Winfield, Joy; Pradhan, Jaya; Mustkov, Vesco; McDonald, Jasmine A.; Pérez Stable, Eliseo J.; Nápoles, Anna María; Vohra, Nasreen; de Siervi, Adriana; Yates, Clayton; Davis, Melissa B.; Yang, Mei; Tsai, Yien Che; Weissman, Allan M.; Gardner, Kevin
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Women of African ancestry suffer higher rates of breast cancer mortality compared with all other groups in the United States. Though the precise reasons for these disparities remain unclear, many recent studies have implicated a role for differences in tumor biology. Using an epitope-validated antibody against the endoplasmic reticulum-associated E3 ligase, gp78, we show that elevated levels of gp78 in patient breast cancer cells predict poor survival. Moreover, high levels of gp78 are associated with poor outcomes in both ER+ and ER- tumors, and breast cancers expressing elevated amounts of gp78 protein are enriched in gene expression pathways that influence cell cycle, metabolism, receptor-mediated signaling, and cell stress response pathways. In multivariate analysis adjusted for subtype and grade, gp78 protein is an independent predictor of poor outcomes in women of African ancestry. Furthermore, gene expression signatures, derived from patients stratified by gp78 protein expression, are strong predictors of recurrence and pathological complete response in retrospective clinical trial data and share many common features with gene sets previously identified to be overrepresented in breast cancers based on race. These findings implicate a prominent role for gp78 in tumor progression and offer insights into our understanding of racial differences in breast cancer outcomes.
Fil: Singhal, Sandeep K.. No especifíca;
Fil: Byun, Jung S.. National Institutes of Health; Estados Unidos
Fil: Yan, Tingfen. National Institutes of Health; Estados Unidos
Fil: Yancey, Ryan. Columbia University; Estados Unidos
Fil: Caban, Ambar. Columbia University; Estados Unidos
Fil: Hernandez, Sara Gil. National Institutes of Health; Estados Unidos
Fil: Bufford, Sediqua. No especifíca;
Fil: Hewitt, Stephen M.. No especifíca;
Fil: Winfield, Joy. Columbia University; Estados Unidos
Fil: Pradhan, Jaya. Columbia University; Estados Unidos
Fil: Mustkov, Vesco. Columbia University; Estados Unidos
Fil: McDonald, Jasmine A.. No especifíca;
Fil: Pérez Stable, Eliseo J.. National Institutes of Health; Estados Unidos
Fil: Nápoles, Anna María. National Institutes of Health; Estados Unidos
Fil: Vohra, Nasreen. No especifíca;
Fil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Yates, Clayton. No especifíca;
Fil: Davis, Melissa B.. No especifíca;
Fil: Yang, Mei. No especifíca;
Fil: Tsai, Yien Che. No especifíca;
Fil: Weissman, Allan M.. No especifíca;
Fil: Gardner, Kevin. Columbia University; Estados Unidos
Materia
GP78
BREAST CANCER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/215952
Acceder
id CONICETDig_cff5484f2ac58fab69e8d99d0c88162e
oai_identifier_str oai:ri.conicet.gov.ar:11336/215952
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on raceSinghal, Sandeep K.Byun, Jung S.Yan, TingfenYancey, RyanCaban, AmbarHernandez, Sara GilBufford, SediquaHewitt, Stephen M.Winfield, JoyPradhan, JayaMustkov, VescoMcDonald, Jasmine A.Pérez Stable, Eliseo J.Nápoles, Anna MaríaVohra, Nasreende Siervi, AdrianaYates, ClaytonDavis, Melissa B.Yang, MeiTsai, Yien CheWeissman, Allan M.Gardner, KevinGP78BREAST CANCERhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Women of African ancestry suffer higher rates of breast cancer mortality compared with all other groups in the United States. Though the precise reasons for these disparities remain unclear, many recent studies have implicated a role for differences in tumor biology. Using an epitope-validated antibody against the endoplasmic reticulum-associated E3 ligase, gp78, we show that elevated levels of gp78 in patient breast cancer cells predict poor survival. Moreover, high levels of gp78 are associated with poor outcomes in both ER+ and ER- tumors, and breast cancers expressing elevated amounts of gp78 protein are enriched in gene expression pathways that influence cell cycle, metabolism, receptor-mediated signaling, and cell stress response pathways. In multivariate analysis adjusted for subtype and grade, gp78 protein is an independent predictor of poor outcomes in women of African ancestry. Furthermore, gene expression signatures, derived from patients stratified by gp78 protein expression, are strong predictors of recurrence and pathological complete response in retrospective clinical trial data and share many common features with gene sets previously identified to be overrepresented in breast cancers based on race. These findings implicate a prominent role for gp78 in tumor progression and offer insights into our understanding of racial differences in breast cancer outcomes.Fil: Singhal, Sandeep K.. No especifíca;Fil: Byun, Jung S.. National Institutes of Health; Estados UnidosFil: Yan, Tingfen. National Institutes of Health; Estados UnidosFil: Yancey, Ryan. Columbia University; Estados UnidosFil: Caban, Ambar. Columbia University; Estados UnidosFil: Hernandez, Sara Gil. National Institutes of Health; Estados UnidosFil: Bufford, Sediqua. No especifíca;Fil: Hewitt, Stephen M.. No especifíca;Fil: Winfield, Joy. Columbia University; Estados UnidosFil: Pradhan, Jaya. Columbia University; Estados UnidosFil: Mustkov, Vesco. Columbia University; Estados UnidosFil: McDonald, Jasmine A.. No especifíca;Fil: Pérez Stable, Eliseo J.. National Institutes of Health; Estados UnidosFil: Nápoles, Anna María. National Institutes of Health; Estados UnidosFil: Vohra, Nasreen. No especifíca;Fil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Yates, Clayton. No especifíca;Fil: Davis, Melissa B.. No especifíca;Fil: Yang, Mei. No especifíca;Fil: Tsai, Yien Che. No especifíca;Fil: Weissman, Allan M.. No especifíca;Fil: Gardner, Kevin. Columbia University; Estados UnidosAmerican Society for Clinical Investigation2022-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/215952Singhal, Sandeep K.; Byun, Jung S.; Yan, Tingfen; Yancey, Ryan; Caban, Ambar; et al.; Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race; American Society for Clinical Investigation; JCI Insight; 7; 13; 7-2022; 1-192379-3708CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://insight.jci.org/articles/view/157465info:eu-repo/semantics/altIdentifier/doi/10.1172/jci.insight.157465info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:39Zoai:ri.conicet.gov.ar:11336/215952instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:01:39.708CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race
title Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race
spellingShingle Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race
Singhal, Sandeep K.
GP78
BREAST CANCER
title_short Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race
title_full Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race
title_fullStr Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race
title_full_unstemmed Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race
title_sort Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race
dc.creator.none.fl_str_mv Singhal, Sandeep K.
Byun, Jung S.
Yan, Tingfen
Yancey, Ryan
Caban, Ambar
Hernandez, Sara Gil
Bufford, Sediqua
Hewitt, Stephen M.
Winfield, Joy
Pradhan, Jaya
Mustkov, Vesco
McDonald, Jasmine A.
Pérez Stable, Eliseo J.
Nápoles, Anna María
Vohra, Nasreen
de Siervi, Adriana
Yates, Clayton
Davis, Melissa B.
Yang, Mei
Tsai, Yien Che
Weissman, Allan M.
Gardner, Kevin
author Singhal, Sandeep K.
author_facet Singhal, Sandeep K.
Byun, Jung S.
Yan, Tingfen
Yancey, Ryan
Caban, Ambar
Hernandez, Sara Gil
Bufford, Sediqua
Hewitt, Stephen M.
Winfield, Joy
Pradhan, Jaya
Mustkov, Vesco
McDonald, Jasmine A.
Pérez Stable, Eliseo J.
Nápoles, Anna María
Vohra, Nasreen
de Siervi, Adriana
Yates, Clayton
Davis, Melissa B.
Yang, Mei
Tsai, Yien Che
Weissman, Allan M.
Gardner, Kevin
author_role author
author2 Byun, Jung S.
Yan, Tingfen
Yancey, Ryan
Caban, Ambar
Hernandez, Sara Gil
Bufford, Sediqua
Hewitt, Stephen M.
Winfield, Joy
Pradhan, Jaya
Mustkov, Vesco
McDonald, Jasmine A.
Pérez Stable, Eliseo J.
Nápoles, Anna María
Vohra, Nasreen
de Siervi, Adriana
Yates, Clayton
Davis, Melissa B.
Yang, Mei
Tsai, Yien Che
Weissman, Allan M.
Gardner, Kevin
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GP78
BREAST CANCER
topic GP78
BREAST CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Women of African ancestry suffer higher rates of breast cancer mortality compared with all other groups in the United States. Though the precise reasons for these disparities remain unclear, many recent studies have implicated a role for differences in tumor biology. Using an epitope-validated antibody against the endoplasmic reticulum-associated E3 ligase, gp78, we show that elevated levels of gp78 in patient breast cancer cells predict poor survival. Moreover, high levels of gp78 are associated with poor outcomes in both ER+ and ER- tumors, and breast cancers expressing elevated amounts of gp78 protein are enriched in gene expression pathways that influence cell cycle, metabolism, receptor-mediated signaling, and cell stress response pathways. In multivariate analysis adjusted for subtype and grade, gp78 protein is an independent predictor of poor outcomes in women of African ancestry. Furthermore, gene expression signatures, derived from patients stratified by gp78 protein expression, are strong predictors of recurrence and pathological complete response in retrospective clinical trial data and share many common features with gene sets previously identified to be overrepresented in breast cancers based on race. These findings implicate a prominent role for gp78 in tumor progression and offer insights into our understanding of racial differences in breast cancer outcomes.
Fil: Singhal, Sandeep K.. No especifíca;
Fil: Byun, Jung S.. National Institutes of Health; Estados Unidos
Fil: Yan, Tingfen. National Institutes of Health; Estados Unidos
Fil: Yancey, Ryan. Columbia University; Estados Unidos
Fil: Caban, Ambar. Columbia University; Estados Unidos
Fil: Hernandez, Sara Gil. National Institutes of Health; Estados Unidos
Fil: Bufford, Sediqua. No especifíca;
Fil: Hewitt, Stephen M.. No especifíca;
Fil: Winfield, Joy. Columbia University; Estados Unidos
Fil: Pradhan, Jaya. Columbia University; Estados Unidos
Fil: Mustkov, Vesco. Columbia University; Estados Unidos
Fil: McDonald, Jasmine A.. No especifíca;
Fil: Pérez Stable, Eliseo J.. National Institutes of Health; Estados Unidos
Fil: Nápoles, Anna María. National Institutes of Health; Estados Unidos
Fil: Vohra, Nasreen. No especifíca;
Fil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Yates, Clayton. No especifíca;
Fil: Davis, Melissa B.. No especifíca;
Fil: Yang, Mei. No especifíca;
Fil: Tsai, Yien Che. No especifíca;
Fil: Weissman, Allan M.. No especifíca;
Fil: Gardner, Kevin. Columbia University; Estados Unidos
description Women of African ancestry suffer higher rates of breast cancer mortality compared with all other groups in the United States. Though the precise reasons for these disparities remain unclear, many recent studies have implicated a role for differences in tumor biology. Using an epitope-validated antibody against the endoplasmic reticulum-associated E3 ligase, gp78, we show that elevated levels of gp78 in patient breast cancer cells predict poor survival. Moreover, high levels of gp78 are associated with poor outcomes in both ER+ and ER- tumors, and breast cancers expressing elevated amounts of gp78 protein are enriched in gene expression pathways that influence cell cycle, metabolism, receptor-mediated signaling, and cell stress response pathways. In multivariate analysis adjusted for subtype and grade, gp78 protein is an independent predictor of poor outcomes in women of African ancestry. Furthermore, gene expression signatures, derived from patients stratified by gp78 protein expression, are strong predictors of recurrence and pathological complete response in retrospective clinical trial data and share many common features with gene sets previously identified to be overrepresented in breast cancers based on race. These findings implicate a prominent role for gp78 in tumor progression and offer insights into our understanding of racial differences in breast cancer outcomes.
publishDate 2022
dc.date.none.fl_str_mv 2022-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/215952
Singhal, Sandeep K.; Byun, Jung S.; Yan, Tingfen; Yancey, Ryan; Caban, Ambar; et al.; Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race; American Society for Clinical Investigation; JCI Insight; 7; 13; 7-2022; 1-19
2379-3708
CONICET Digital
CONICET
url http://hdl.handle.net/11336/215952
identifier_str_mv Singhal, Sandeep K.; Byun, Jung S.; Yan, Tingfen; Yancey, Ryan; Caban, Ambar; et al.; Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race; American Society for Clinical Investigation; JCI Insight; 7; 13; 7-2022; 1-19
2379-3708
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://insight.jci.org/articles/view/157465
info:eu-repo/semantics/altIdentifier/doi/10.1172/jci.insight.157465
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Clinical Investigation
publisher.none.fl_str_mv American Society for Clinical Investigation
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269709541572608
score 13.13397

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