PXD049435

PXD049435 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling identifies muscle-invasive bladder cancers with distinct biology and responses to platinum-based chemotherapy
Description	Platinum-based neoadjuvant chemotherapy (NAC) prior to radical cystectomy is the preferred treatment for muscle-invasive bladder cancer (MIBC) despite modest survival benefit and significant associated toxicities. Here, we profiled the global proteome of MIBC tumours pre- and post-NAC treatment using archival formalin-fixed paraffin-embedded tissue. We identified four pre-NAC proteomic clusters with distinct biology and response to therapy, and overlaid these with transcriptomic subtypes and immunohistochemistry. We observed proteomic plasticity post-NAC that was associated with increased extracellular matrix and reduced keratinization compared to pre-NAC. Post-NAC clusters appeared to be differentially enriched for druggable proteins. For example, MTOR, and PARP were over-expressed at the protein level in tumours identified as neuronal-like. In addition, we determined that high intra-tumour proteome heterogeneity in pre-NAC tissue was associated with worse prognosis. Our work highlights new aspects of MIBC tumour biology associated with clinical outcomes, and suggests new therapeutic targets based on proteomic clusters.
HostingRepository	PRIDE
AnnounceDate	2025-02-11
AnnouncementXML	Submission_2025-02-11_09:01:14.057.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gian Luca Negri
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-16 14:57:25	ID requested
⏵ 1	2025-02-11 09:01:15	announced

10.1038/s41467-024-55665-1;

Contreras-Sanz A, Negri GL, Reike MJ, Oo HZ, Scurll JM, Spencer SE, Nielsen K, Ikeda K, Wang G, Jackson CL, Gupta S, Roberts ME, Berman DM, Seiler R, Morin GB, Black PC, Proteomic profiling identifies muscle-invasive bladder cancers with distinct biology and responses to platinum-based chemotherapy. Nat Commun, 16(1):1240(2025) [pubmed]

submitter keyword: bladder cancer, mibc

Gregg Morin
contact affiliation	Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver V5Z 1L3, Canada.
contact email	gmorin@bcgsc.ca
lab head
Gian Luca Negri
contact affiliation	Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver V5Z 1L3, Canada.
contact email	gnegri@bcgsc.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/2025/02/PXD049435

PRIDE project URI

• PRIDE
  1. PXD049435
     1. Label: PRIDE project
     2. Name: Proteomic profiling identifies muscle-invasive bladder cancers with distinct biology and responses to platinum-based chemotherapy