In vivo phosphoproteomics reveals kinase activity profiles that predict treatment outcome in triple-negative breast cancer

Ivana Zagorac, Sara Fernandez-Gaitero, Renske Penning, Harm Post, Maria J. Bueno, Silvana Mouron, Luis Manso, Manuel M. Morente, Soledad Alonso, Violeta Serra, Javier Muñoz, Gonzalo Gómez-López, Jose Francisco Lopez-Acosta, Veronica Jimenez-Renard, Albert Gris-Oliver, Fatima Al-Shahrour, Elena Piñeiro-Yañez, Jose Luis Montoya-Suarez, Juan V. Apala, Amalia Moreno-Torres, Ramon Colomer, Ana Dopazo, Albert J. R. Heck, Maarten Altelaar and Miguel Quintela-Fandino ()
Additional contact information
Ivana Zagorac: CNIO – Spanish National Cancer Research Center
Sara Fernandez-Gaitero: CNIO – Spanish National Cancer Research Center
Renske Penning: Utrecht University
Harm Post: Utrecht University
Maria J. Bueno: CNIO – Spanish National Cancer Research Center
Silvana Mouron: CNIO – Spanish National Cancer Research Center
Luis Manso: Medical Oncology
Manuel M. Morente: Biobank, CNIO – Spanish National Cancer Research Center
Soledad Alonso: Hospital Universitario de Guadalajara
Violeta Serra: VHIO - Vall d’Hebron Institute of Oncology
Javier Muñoz: CNIO – Spanish National Cancer Research Center
Gonzalo Gómez-López: CNIO – Spanish National Cancer Research Center
Jose Francisco Lopez-Acosta: CNIO – Spanish National Cancer Research Center
Veronica Jimenez-Renard: CNIO – Spanish National Cancer Research Center
Albert Gris-Oliver: VHIO - Vall d’Hebron Institute of Oncology
Fatima Al-Shahrour: CNIO – Spanish National Cancer Research Center
Elena Piñeiro-Yañez: CNIO – Spanish National Cancer Research Center
Jose Luis Montoya-Suarez: Hospital Nacional Guillermo Almenara Irigoyen – ESSALUD
Juan V. Apala: CNIO – Spanish National Cancer Research Center
Amalia Moreno-Torres: Hospital Universitario de Fuenlabrada
Ramon Colomer: Hospital La Princesa
Ana Dopazo: CNIC - Spanish National Center for Cardiovascular Research
Albert J. R. Heck: Utrecht University
Maarten Altelaar: Utrecht University
Miguel Quintela-Fandino: CNIO – Spanish National Cancer Research Center

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-05742-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05742-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-05742-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().