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A novel approach to triplenegative breast cancer molecular classification reveals a luminal immune-positive subgroup with good prognoses

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dc.contributor.authorPrado Vázquez, Guillermo
dc.contributor.authorGámez Pozo, Ángelo
dc.contributor.authorTrilla Fuertes, Lucía
dc.contributor.authorZapater Moros, Andrea
dc.contributor.authorFerrer Gómez, María
dc.contributor.authorDíaz Almirón, Mariana
dc.contributor.authorLópez Vacas, Rocío
dc.contributor.authorMaín, Paloma
dc.contributor.authorFeliu Batlle, Jaime
dc.contributor.authorZamora Auñón, Pilar
dc.contributor.authorEspinosa, Enrique
dc.contributor.authorFresno Vara, Juan Ángel
dc.contributor.authorMartín Arevalillo, Jorge
dc.contributor.authorNavarro Veguillas, Hilario
dc.date.accessioned2024-05-20T11:24:43Z
dc.date.available2024-05-20T11:24:43Z
dc.date.issued2019-02-07
dc.description.abstractTriple-negative breast cancer is a heterogeneous disease characterized by a lack of hormonal receptors and HER2 overexpression. It is the only breast cancer subgroup that does not benefit from targeted therapies, and its prognosis is poor. Several studies have developed specific molecular classifications for triple-negative breast cancer. However, these molecular subtypes have had little impact in the clinical setting. Gene expression data and clinical information from 494 triple-negative breast tumors were obtained from public databases. First, a probabilistic graphical model approach to associate gene expression profiles was performed. Then, sparse k-means was used to establish a new molecular classification. Results were then verified in a second database including 153 triple-negative breast tumors treated with neoadjuvant chemotherapy. Clinical and gene expression data from 494 triple-negative breast tumors were analyzed. Tumors in the dataset were divided into four subgroups (luminal-androgen receptor expressing, basal, claudin-low and claudin-high), using the cancer stem cell hypothesis as reference. These four subgroups were defined and characterized through hierarchical clustering and probabilistic graphical models and compared with previously defined classifications. In addition, two subgroups related to immune activity were defined. This immune activity showed prognostic value in the whole cohort and in the luminal subgroup. The claudin-high subgroup showed poor response to neoadjuvant chemotherapy. Through a novel analytical approach we proved that there are at least two independent sources of biological information: cellular and immune. Thus, we developed two different and overlapping triple-negative breast cancer classifications and showed that the luminal immune-positive subgroup had better prognoses than the luminal immune-negative. Finally, this work paves the way for using the defined classifications as predictive features in the neoadjuvant scenario.en
dc.description.versionversión publicada
dc.identifier.doihttp://doi.org/10.1038/s41598-018-38364-y
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/20.500.14468/11924
dc.journal.titleScientific Reports
dc.journal.volume9
dc.language.isoen
dc.publisherSpringer nature
dc.relation.centerFacultad de Ciencias
dc.relation.departmentEstadística, Investigación Operativa y Cálculo Numérico
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0
dc.titleA novel approach to triplenegative breast cancer molecular classification reveals a luminal immune-positive subgroup with good prognoseses
dc.typejournal articleen
dc.typeartículoes
dspace.entity.typePublication
person.familyNameMartín Arevalillo
person.familyNameNavarro Veguillas
person.givenNameJorge
person.givenNameHilario
person.identifier.orcid0000-0003-1944-3699
relation.isAuthorOfPublicationea1c092a-eceb-49c8-abb7-d4d52f53930a
relation.isAuthorOfPublicationb4ef2ce4-140a-4dfd-b87f-363a7a9136e5
relation.isAuthorOfPublication.latestForDiscoveryea1c092a-eceb-49c8-abb7-d4d52f53930a
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