PXD010133

PXD010133 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling of diffuse gliomas defines clinically and histopathologically relevant disease subtypes
Description	Background: Molecular profiling of diffuse gliomas has provided significant insights into the pathogenesis, classification and prognostication of these malignancies. However, previous molecular studies of glioma have largely focused on genomic readouts and targeted proteomic profiling technologies. Consequently, proteomic and downstream functional landscape of gliomas in general, and molecular subgroups in particular, remains largely unexplored. Here, we utilize liquid chromatography tandem mass spectrometry to profile genomically-defined cohorts of gliomas spanning the full range of World Health Organization (WHO) grades. Methods: Bulk frozen tissue and purified micro-dissected regions from formalin-fixed paraffin-embedded (FFPE) tissues were assembled and utilized to define robust proteomic signatures of both low grade, infiltrative and high-grade tumors. As a final analysis, primary tumor tissue was compared with both IDH-mutated and IDH-wildtype glioblastoma stem cell (GSC) lines to further overcome tissue heterogeneity and pinpoint proteins differences likely arising in the relevant glial cellular drivers of tumor development. Results: In aggregate, 5,496 unique proteins over 3 glioma cohorts were identified, and span common molecular subclasses based on IDH and 1p19q co-deletion status and all four WHO grades. Supervised clustering highlights substantial proteome and systems-level pathway differences between different genetically defined glioma subtypes and WHO grades. By using bulk tumor statistical analysis, 833 proteins distinguish different WHO grade tumors, while FFPE tumor dissection reveals 287 proteins in GBMs with abundance changes according to IDH mutation status. Using our integrative approach, calcium signaling, proteins of the endoplasmic reticulum and extracellular integrin proteins are most conserved proteomic markers that distinguish aggressive, IDH-wt, from IDH-mut GBM tumors in primary and tissue culture models gliomagenesis. Conclusions: This proteomic survey provides the largest and most diverse unbiased protein-based brain tumor resource to date. Current treatments for glial tumors are largely non-specific and overlap between genomic subtypes and WHO grades. Our analysis provides early insight into the vast downstream and epigenetic protein-level differences within this molecular framework. Given the central position proteins occupy in driving biology and phenotype, further characterization of the substantial proteomic diversity that exist between the molecular subtypes and grades of gliomas, proteomics may help define more personalized prognostic and predictive biomarkers for precision care.
HostingRepository	PRIDE
AnnounceDate	2019-07-30
AnnouncementXML	Submission_2019-07-30_03:05:56.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ugljesa Djuric
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-14 09:01:15	ID requested
⏵ 1	2019-07-30 03:05:57	announced

Dataset with its publication pending

curator keyword: Technical, Biological

submitter keyword: Proteome-wide analysis, gliomas, classification, mass spectrometry, biomarkers, neuro-oncology

Phedias Diamandis
contact affiliation	UHN
contact email	p.diamandis@mail.utoronto.ca
lab head
Ugljesa Djuric
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/2019/07/PXD010133

PRIDE project URI

• PRIDE
  1. PXD010133
     1. Label: PRIDE project
     2. Name: Proteomic profiling of diffuse gliomas defines clinically and histopathologically relevant disease subtypes