PXD005544-1

PXD005544 is an original dataset announced via ProteomeXchange.

Title	Downregulation of antigen presentation-associated pathway proteins in poor outcome triple-negative breast cancer patient tumors
Description	Triple-negative breast cancer (TNBC) is a heterogeneous subtype with varying disease outcomes. Tumor infiltrating lymphocytes (TILs) are frequent in TNBC and have been shown to correlate with outcome, suggesting an immunogenic component in this subtype. However, other factors, intrinsic to the cancer cells, may also influence outcome. To identify proteins and molecular pathways associated with recurrence in TNBC, 34 formalin-fixed paraffin-embedded (FFPE) primary TNBC tumors were investigated by global proteomic profiling using TMT-HILIC-LC-MS/MS. Approximately half of the patients were lymph node-negative and remained free of local or distant metastasis within 10 years follow-up, while the other half developed distant metastasis. Proteomic profiling identified >4000 proteins, of which 63 exhibited altered expression in primary tumors of recurrence versus recurrence-free patients. Importantly, down-regulation of proteins in the major histocompatibility complex (MHC) class I antigen presentation pathways were enriched, including TAP1, TAP2, CALR, HLA-A, ERAP1 and TAPBP, and were associated with significantly shorter recurrence-free and overall survival. In addition, proteins involved in cancer cell proliferation and growth, including GBP1, RAD23B, WARS and STAT1, also exhibited altered expression in primary tumors of recurrence versus recurrence-free patients. The association between the antigen-presentation pathway and outcome were validated in a second sample set of 10 primary TNBC tumors and corresponding metastases using proteomics and in a large public gene expression database of 249 TNBC and 580 basal-like breast cancer cases. Our study demonstrates that down-regulation of antigen presentation is a key mechanism for TNBC cells to avoid immune surveillance, allowing continued growth and spread.
HostingRepository	PRIDE
AnnounceDate	2018-10-26
AnnouncementXML	Submission_2018-10-26_12:14:14.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martin Haar Pedersen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-12-12 01:13:51	ID requested
⏵ 1	2018-10-26 12:14:16	announced
2	2024-10-22 04:35:07	announced	2024-10-22: Updated project metadata.

Pedersen MH, Hood BL, Beck HC, Conrads TP, Ditzel HJ, Leth-Larsen R, Downregulation of antigen presentation-associated pathway proteins is linked to poor outcome in triple-negative breast cancer patient tumors. Oncoimmunology, 6(5):e1305531(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: Triple-negative breast cancer, basal-like breast cancer, mass spectrometry, proteomics, formalin-fixed paraffin embedded, major histocompatibility complex, MHC class I antigen presentation pathway, biomarker

Henrik Ditzel
contact affiliation	Professor, Head of Cancer Research, University of Southern Denmark
contact email	henrik.ditzel@health.sdu.dk
lab head
Martin Haar Pedersen
contact affiliation	University of Southern Denmark
contact email	mhpedersen@health.sdu.dk
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/2018/10/PXD005544

PRIDE project URI

• PRIDE
  1. PXD005544
     1. Label: PRIDE project
     2. Name: Downregulation of antigen presentation-associated pathway proteins in poor outcome triple-negative breast cancer patient tumors