PXD029290

PXD029290 is an original dataset announced via ProteomeXchange.

Title	Topographic mapping of the glioblastoma proteome reveals a triple axis model of intra-tumoral heterogeneity
Description	Glioblastoma (GBM) is an aggressive form of brain cancer with well-established patterns of intra-tumoral heterogeneity implicated in treatment resistance, recurrence and progression. While regional and single cell transcriptomic variations of GBM have been recently resolved, downstream phenotype-level proteomic programs have yet to be assigned to specific niches. Here, we leverage mass spectrometry to spatially align abundance levels of 4,794 proteins to GBM’s hallmark histomorphologic niches across 20 patients and define distinct molecular programs operational within these regional tumor compartments. Using machine learning, we overlay concordant transcriptional information, and define two distinct proteogenomic programs, MYC- and KRAS-axis hereon, that cooperate with hypoxia to produce a tri-dimensional model of intra-tumoral heterogeneity. Importantly, we show using multiple cohorts, that GBMs with an enhanced KRAS component harbor a more clinically aggressive and infiltrative phenotype. Conversely, tumor cells enriched along the MYC axis where mutually exclusive and had a distinct proliferative program. Moreover, by applying both experimental and computational approaches to link each of these distinct molecular axes with potential pharmacological therapies, we highlight differential drug sensitivities and a notable relative chemoresistance in GBM cell lines with enhanced KRAS programs. Importantly, pharmacological differences were less evident when using traditional expression-based subgroups supporting thattopographic phenotypic mapping ofGBM, and the proposed axes may provide new insights for targeting heterogeneity and overcoming therapy resistance in this aggressive disease.
HostingRepository	PRIDE
AnnounceDate	2023-04-11
AnnouncementXML	Submission_2023-04-11_06:33:07.981.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	UgljesaDjuric
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-22 06:57:13	ID requested
1	2021-11-02 06:40:50	announced
⏵ 2	2023-04-11 06:33:08	announced	2023-04-11: Updated project metadata.

Lam KHB, Leon AJ, Hui W, Lee SC, Batruch I, Faust K, Klekner A, Hut, ó, czki G, Koritzinsky M, Richer M, Djuric U, Diamandis P, Topographic mapping of the glioblastoma proteome reveals a triple-axis model of intra-tumoral heterogeneity. Nat Commun, 13(1):116(2022) [pubmed]

submitter keyword: proteomics,GBM, mass spectrometry

PhediasDiamandis
contact affiliation	Princess Margaret Hospital University of Toronto University Health Network
contact email	phedias.diamandis@uhn.ca
lab head
UgljesaDjuric
contact affiliation	Mt. Sinai Hospital
contact email	ugljesa.djuric@mail.utoronto.ca
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/11/PXD029290

PRIDE project URI

• PRIDE
  1. PXD029290
     1. Label: PRIDE project
     2. Name: Topographic mapping of the glioblastoma proteome reveals a triple axis model of intra-tumoral heterogeneity