2026-06-14T03:30:34Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65272025-03-20T10:47:26Zcom_20.500.12105_2173com_20.500.12105_2051com_20.500.12105_19604col_20.500.12105_19597col_20.500.12105_19607
Repisalud
author
Zagorac, Ivana
author
Fernandez-Gaitero, Sara
author
Penning, Renske
author
Post, Harm
author
Bueno Verdejo, Maria Jose
author
Mouron, Silvana Andrea
author
Manso, Luis
author
Morente Gallego, Manuel M
author
Alonso, Soledad
author
Serra, Violeta
author
Muoz Peralta, Javier
author
Gomez Lopez, Gonzalo
author
Lopez-Acosta, Jose Francisco
author
Jimenez-Renard, Veronica
author
Gris-Oliver, Albert
author
Al-Shahrour, Fatima
author
Piñeiro-Yañez, Elena
author
Montoya-Suarez, Jose Luis
author
Apala, Juan V
author
Moreno-Torres, Amalia
author
Colomer, Ramon
author
Dopazo, Ana
author
Heck, Albert J R
author
Altelaar, Maarten
author
Quintela Fandino, Miguel Angel
funder
Unión Europea. Comisión Europea
funder
Dutch Research Council (Holanda)
funder
CRIS contra el Cáncer
funder
Asociación Española Contra el Cáncer
funder
Fundación La Caixa
funder
Instituto de Salud Carlos III
2018-10-25T10:22:43Z
2018-10-25T10:22:43Z
2018-08-29
Nat Commun. 2018; 9(1): 3501.
10.1038/s41467-018-05742-z
2041-1723
2041-1723
Nature communications
30158526
http://hdl.handle.net/20.500.12105/6527
Triple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, we use high-throughput phosphoproteomics to build a functional TNBC taxonomy. A cluster of 159 phosphosites is upregulated in relapsed cases of a training set (n = 34 patients), with 11 hyperactive kinases accounting for this phosphoprofile. A mass-spectrometry-to-immunohistochemistry translation step, assessing 2 independent validation sets, reveals 6 kinases with preserved independent prognostic value. The kinases split the validation set into two patterns: one without hyperactive kinases being associated with a >90% relapse-free rate, and the other one showing ≥1 hyperactive kinase and being associated with an up to 9.5-fold higher relapse risk. Each kinase pattern encompasses different mutational patterns, simplifying mutation-based taxonomy. Drug regimens designed based on these 6 kinases show promising antitumour activity in TNBC cell lines and patient-derived xenografts. In summary, the present study elucidates phosphosites and kinases implicated in TNBC and suggests a target-based clinical classification system for TNBC.
eng
SET ENRICHMENT ANALYSIS
C-KIT
PEPTIDE IDENTIFICATION
THERAPEUTIC TARGETS
SOMATIC MUTATIONS
TUMOR XENOGRAFTS
INHIBITION
EXPRESSION
LANDSCAPE
In vivo phosphoproteomics reveals kinase activity profiles that predict treatment outcome in triple-negative breast cancer
journal article
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