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

Mendaza Lainez, Saioa; Guerrero Setas, David; Monreal Santesteban, Iñaki; Ulazia Garmendia, Ane; Córdoba Iturriagagoitia, Alicia; Cruz, Susana de la; Martín Sánchez, Esperanza

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

dc.contributor.author	Mendaza Lainez, Saioa
dc.contributor.author	Guerrero Setas, David
dc.contributor.author	Monreal Santesteban, Iñaki
dc.contributor.author	Ulazia Garmendia, Ane
dc.contributor.author	Córdoba Iturriagagoitia, Alicia
dc.contributor.author	Cruz, Susana de la
dc.contributor.author	Martín Sánchez, Esperanza
dc.contributor.department	Ciencias de la Salud	es_ES
dc.contributor.department	Osasun Zientziak	eu
dc.contributor.funder	Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa	es
dc.date.accessioned	2022-04-05T11:01:07Z
dc.date.available	2022-04-05T11:01:07Z
dc.date.issued	2021
dc.description.abstract	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.	en
dc.description.sponsorship	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).
dc.format.extent	14 p.
dc.format.mimetype	application/pdf	en
dc.identifier.doi	10.3390/biomedicines9101394
dc.identifier.issn	2227-9059
dc.identifier.uri	https://academica-e.unavarra.es/handle/2454/42653
dc.language.iso	eng	en
dc.publisher	MDPI
dc.relation.ispartof	Biomedicines, 9 (10)	en
dc.relation.projectID	info:eu-repo/grantAgreement/MINECO//PTA2015-11895-I/ES/
dc.relation.publisherversion	https://doi.org/10.3390/biomedicines9101394
dc.rights	© 2021 by the authors. Creative Commons Attribution 4.0 International	en
dc.rights.accessRights	info:eu-repo/semantics/openAccess
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/
dc.subject	Diagnosis	en
dc.subject	Diagnosis signature	en
dc.subject	DNA methylation	en
dc.subject	Epigenetic biomarker	en
dc.subject	Triple-negative breast cancer	en
dc.title	A DNA methylation-based gene signature can predict triple-negative breast cancer diagnosis	en
dc.type	info:eu-repo/semantics/article
dc.type.version	info:eu-repo/semantics/publishedVersion
dspace.entity.type	Publication
relation.isAuthorOfPublication	ab42c33f-1671-49dc-ab31-89b9cac82366
relation.isAuthorOfPublication.latestForDiscovery	ab42c33f-1671-49dc-ab31-89b9cac82366