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PXD008012

PXD008012 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIn vivo phosphoproteomics reveals kinase activity profiles that predict treatment outcome in triple-negative breast cancer
DescriptionTriple-negative breast cancer (TNBC) lacks prognostic and predictive markers. We used high-throughput phosphoproteomics to build a functional TNBC taxonomy. A cluster of 159 phosphosites was upregulated in relapsed cases of a training set (n=34 patients). Eleven hyperactive kinases accounted for this phosphoprofile. A massspectrometry-to-immunohistochemistry translation step that assessed 113 TNBC validation specimens revealed that 6/12 kinases (PRKCE, KIT, PNKP, ERK, CDK6, and P70S6K) preserved independent prognostic value. The kinases split the validation set into two patterns: one (0/6 hyperactive kinases; 29% of the patients) associated with a 93.5% cure rate. The other (≥1 hyperactive kinase; 37 subpatterns) was associated with a 9.5-fold higher relapse risk. Each kinase pattern agglutinated different mutational patterns. Drug regimens designed based on these six kinases showed synergistic activity in vitro and in vivo. Our results elucidated novel phosphosites/kinases that are implicated in TNBC and provide a ready-to-use, actionable target-based clinical classification system for TNBC
HostingRepositoryPRIDE
AnnounceDate2018-07-23
AnnouncementXMLSubmission_2019-03-07_05:40:01.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJavier Muñoz
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-10-23 02:04:44ID requested
12018-07-19 03:16:40announced
22018-07-24 05:27:35announcedUpdated contact info
32019-03-07 05:40:03announcedUpdated publication reference for PubMed record(s): 30158526.
Publication List
Zagorac I, Fernandez-Gaitero S, Penning R, Post H, Bueno MJ, Mouron S, Manso L, Morente MM, Alonso S, Serra V, Mu, ñ, oz J, G, ó, mez-L, ó, pez G, Lopez-Acosta JF, Jimenez-Renard V, Gris-Oliver A, Al-Shahrour F, Pi, ñ, eiro-Ya, ñ, ez E, Montoya-Suarez JL, Apala JV, Moreno-Torres A, Colomer R, Dopazo A, Heck AJR, Altelaar M, Quintela-Fandino M, In vivo phosphoproteomics reveals kinase activity profiles that predict treatment outcome in triple-negative breast cancer. Nat Commun, 9(1):3501(2018) [pubmed]
Keyword List
ProteomeXchange project tag: PRIME-XS Project
curator keyword: Biomedical
submitter keyword: triple negative breast cancer, phophoproteomics, kinases
Contact List
Miguel Quintela-Fandino
contact affiliationBreast Cancer Clinical Research Unit, CNIO, Spanish National Cancer Research Centre, Spain
contact emailmquintela@cnio.es
lab head
Javier Muñoz
contact affiliationBreast Cancer Clinical Research Unit, CNIO, Spanish National Cancer Research Centre, Spain
contact emailjmunozpe@cnio.es
dataset submitter
Full Dataset Link List
Dataset FTP location
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