A DNA methylation-based gene signature can predict triple-negative breast cancer diagnosis

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer (BC) subtype and lacks targeted treatment. It is diagnosed by the absence of immunohistochemical expression of several biomarkers, but this method still displays some interlaboratory variability. DNA methylome aberrations are...

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Autores: Mendaza Lainez, Saioa, Guerrero Setas, David, Monreal Santesteban, Iñaki, Ulazia Garmendia, Ane, Córdoba Iturriagagoitia, Alicia, Cruz, Susana de la, Martín Sánchez, Esperanza
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/42653
Acceso en línea:https://hdl.handle.net/2454/42653
Access Level:acceso abierto
Palabra clave:Diagnosis
Diagnosis signature
DNA methylation
Epigenetic biomarker
Triple-negative breast cancer
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spelling A DNA methylation-based gene signature can predict triple-negative breast cancer diagnosisMendaza Lainez, SaioaGuerrero Setas, DavidMonreal Santesteban, IñakiUlazia Garmendia, AneCórdoba Iturriagagoitia, AliciaCruz, Susana de laMartín Sánchez, EsperanzaDiagnosisDiagnosis signatureDNA methylationEpigenetic biomarkerTriple-negative breast cancerTriple-negative breast cancer (TNBC) is the most aggressive breast cancer (BC) subtype and lacks targeted treatment. It is diagnosed by the absence of immunohistochemical expression of several biomarkers, but this method still displays some interlaboratory variability. DNA methylome aberrations are common in BC, thereby methylation profiling could provide the identification of accurate TNBC diagnosis biomarkers. Here, we generated a signature of differentially methylated probes with class prediction ability between 5 non-neoplastic breast and 7 TNBC tissues (error rate = 0.083). The robustness of this signature was corroborated in larger cohorts of additional 58 non-neoplastic breast, 93 TNBC, and 150 BC samples from the Gene Expression Omnibus repository, where it yielded an error rate of 0.006. Furthermore, we validated by pyrosequencing the hypo-methylation of three out of 34 selected probes (FLJ43663, PBX Homeobox 1 (PBX1), and RAS P21 protein activator 3 (RASA3) in 51 TNBC, even at early stages of the disease. Finally, we found significantly lower methylation levels of FLJ43663 in cell free-DNA from the plasma of six TNBC patients than in 15 healthy donors. In conclusion, we report a novel DNA methylation signature with potential predictive value for TNBC diagnosis.This research was funded by a competitive call of the Interreg Sudoe European Regional Development Fund (ONCONET, GT 1.2.) and by the Breast Cancer Patients’ Association of Navarre (SARAY). E.M.-S. received a grant from the Spanish Ministry of Science, Innovation and Universities (PTA2015-11895-I). S.M. was supported by a postdoctoral grant from Public University of Navarre (UPNA).MDPICiencias de la SaludOsasun ZientziakUniversidad Pública de Navarra / Nafarroako Unibertsitate Publikoa2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2454/42653reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarrainstname:Universidad Pública de NavarraInglésinfo:eu-repo/grantAgreement/MINECO//PTA2015-11895-I© 2021 by the authors. Creative Commons Attribution 4.0 Internationalhttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:academica-e.unavarra.es:2454/426532026-06-17T12:41:47Z
dc.title.none.fl_str_mv A DNA methylation-based gene signature can predict triple-negative breast cancer diagnosis
title A DNA methylation-based gene signature can predict triple-negative breast cancer diagnosis
spellingShingle A DNA methylation-based gene signature can predict triple-negative breast cancer diagnosis
Mendaza Lainez, Saioa
Diagnosis
Diagnosis signature
DNA methylation
Epigenetic biomarker
Triple-negative breast cancer
title_short A DNA methylation-based gene signature can predict triple-negative breast cancer diagnosis
title_full A DNA methylation-based gene signature can predict triple-negative breast cancer diagnosis
title_fullStr A DNA methylation-based gene signature can predict triple-negative breast cancer diagnosis
title_full_unstemmed A DNA methylation-based gene signature can predict triple-negative breast cancer diagnosis
title_sort A DNA methylation-based gene signature can predict triple-negative breast cancer diagnosis
dc.creator.none.fl_str_mv Mendaza Lainez, Saioa
Guerrero Setas, David
Monreal Santesteban, Iñaki
Ulazia Garmendia, Ane
Córdoba Iturriagagoitia, Alicia
Cruz, Susana de la
Martín Sánchez, Esperanza
author Mendaza Lainez, Saioa
author_facet Mendaza Lainez, Saioa
Guerrero Setas, David
Monreal Santesteban, Iñaki
Ulazia Garmendia, Ane
Córdoba Iturriagagoitia, Alicia
Cruz, Susana de la
Martín Sánchez, Esperanza
author_role author
author2 Guerrero Setas, David
Monreal Santesteban, Iñaki
Ulazia Garmendia, Ane
Córdoba Iturriagagoitia, Alicia
Cruz, Susana de la
Martín Sánchez, Esperanza
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ciencias de la Salud
Osasun Zientziak
Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
dc.subject.none.fl_str_mv Diagnosis
Diagnosis signature
DNA methylation
Epigenetic biomarker
Triple-negative breast cancer
topic Diagnosis
Diagnosis signature
DNA methylation
Epigenetic biomarker
Triple-negative breast cancer
description Triple-negative breast cancer (TNBC) is the most aggressive breast cancer (BC) subtype and lacks targeted treatment. It is diagnosed by the absence of immunohistochemical expression of several biomarkers, but this method still displays some interlaboratory variability. DNA methylome aberrations are common in BC, thereby methylation profiling could provide the identification of accurate TNBC diagnosis biomarkers. Here, we generated a signature of differentially methylated probes with class prediction ability between 5 non-neoplastic breast and 7 TNBC tissues (error rate = 0.083). The robustness of this signature was corroborated in larger cohorts of additional 58 non-neoplastic breast, 93 TNBC, and 150 BC samples from the Gene Expression Omnibus repository, where it yielded an error rate of 0.006. Furthermore, we validated by pyrosequencing the hypo-methylation of three out of 34 selected probes (FLJ43663, PBX Homeobox 1 (PBX1), and RAS P21 protein activator 3 (RASA3) in 51 TNBC, even at early stages of the disease. Finally, we found significantly lower methylation levels of FLJ43663 in cell free-DNA from the plasma of six TNBC patients than in 15 healthy donors. In conclusion, we report a novel DNA methylation signature with potential predictive value for TNBC diagnosis.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2454/42653
url https://hdl.handle.net/2454/42653
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO//PTA2015-11895-I
dc.rights.none.fl_str_mv © 2021 by the authors. Creative Commons Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © 2021 by the authors. Creative Commons Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
instname:Universidad Pública de Navarra
instname_str Universidad Pública de Navarra
reponame_str Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
collection Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
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repository.mail.fl_str_mv
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