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

Prado-Vázquez, Guillermo, Gámez-Pozo, Angelo, Trilla-Fuertes, Lucía, Arevalillo, Jorge M., Zapater-Moros, Andrea, Ferrer-Gómez, María, Díaz-Almirón, Mariana, López-Vacas, Rocío, Navarro, Hilario, Maín, Paloma, Feliú, Jaime, Zamora, Pilar, Espinosa, Enrique y Fresno Vara, Juan Ángel . (2019) A novel approach to triplenegative breast cancer molecular classification reveals a luminal immune-positive subgroup with good prognoses. Scientific Reports, 9, 1538 (2019)

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Título A novel approach to triplenegative breast cancer molecular classification reveals a luminal immune-positive subgroup with good prognoses
Autor(es) Prado-Vázquez, Guillermo
Gámez-Pozo, Angelo
Trilla-Fuertes, Lucía
Arevalillo, Jorge M.
Zapater-Moros, Andrea
Ferrer-Gómez, María
Díaz-Almirón, Mariana
López-Vacas, Rocío
Navarro, Hilario
Maín, Paloma
Feliú, Jaime
Zamora, Pilar
Espinosa, Enrique
Fresno Vara, Juan Ángel
Materia(s) Estadística
Abstract Triple-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.
Editor(es) Springer nature
Fecha 2019-02-07
Formato application/pdf
Identificador bibliuned:DptoEOICN-FCIE-Articulos-Hnavarro-0005
http://e-spacio.uned.es/fez/view/bibliuned:DptoEOICN-FCIE-Articulos-Hnavarro-0005
DOI - identifier 10.1038/s41598-018-38364-y
ISSN - identifier 2045-2322
Nombre de la revista Scientific Reports
Número de Volumen 9
Publicado en la Revista Scientific Reports, 9, 1538 (2019)
Idioma eng
Versión de la publicación publishedVersion
Tipo de recurso Article
Derechos de acceso y licencia http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
Tipo de acceso Acceso abierto
Notas adicionales The registered version of this article, first published in Scientific Reports, is available online at the publisher's website: Springer nature, https://doi.org/10.1038/s41598-018-38364-y
Notas adicionales La versión registrada de este artículo, publicado por primera vez en Scientific Reports, está disponible en línea en el sitio web del editor: Springer nature, https://doi.org/10.1038/s41598-018-38364-y

 
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Creado: Mon, 29 Jan 2024, 21:47:13 CET