PXD066224

PXD066224 is an original dataset announced via ProteomeXchange.

Title	Proteogenomic characterization of invasive breast tumors in young women
Description	Breast cancer in women <40, accounting for ~5% of all breast cancer cases diagnosed in the U.S., is more aggressive and associated with worse outcomes compared to breast cancer in older women. We performed a first-ever integrated proteogenomic study from a matched cohort of laser-microdissected tumors of 34 young (<40 years) and 34 older (≥60 years) women to identify molecular features that may underlie the worse outcomes in young women. Progression-free interval was shorter in young women, and their tumors were enriched for more aggressive molecular subtypes. Our multi-omic analysis identified distinct clusters in luminal, but not basal-like cancers between age groups. Notably, GATA3 mutations were enriched in luminal tumors from young women, while TP53 and PIK3CA mutations more common in luminal tumors from older women. Young women’s tumors exhibited lower estrogen receptor (ER) expression yet paradoxically enhanced ER response pathways and increased expression of tamoxifen-resistance-associated genes (IRS1, FERMT1). Immune pathway activity and immune scores were lower in tumors from young women, whereas proliferative and MYC pathways were notably elevated, identifying potential therapeutic targets. Transcriptomic data from TCGA and METABRIC confirmed our findings, with 10 of 11 observed pathways corroborated. Finally, differential expression of four immune-related surface proteins also suggested potential age-specific responses of immune-based therapies. Together, these findings may contribute to the understanding of the molecular mechanisms underlying worse outcomes in young women, and offer new insight to therapeutic strategies.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-25_11:42:44.975.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Conrads
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-16 13:03:53	ID requested
⏵ 1	2025-08-25 11:42:45	announced

Raj-Kumar PK, Liu J, Soltis AR, Bateman NW, Chen Q, Sturtz LA, Deyarmin B, Pierobon M, Abulez TA, Praveen-Kumar A, Zhang X, Nguyen T, Yan C, Hu Y, Guion K, Hooke JA, Kovatich AJ, Fantacone-Campbell L, Mostoller B, Kvecher L, Somiari S, Steeg PS, Rajagopal PS, Darcy KM, Lee JSH, Dalgard CL, Conrads TP, Petricoin EF, Meerzaman D, Wilkerson MD, Lin X, Shriver CD, Lipkowitz S, Hu H, Larson C, Blackburn H, Miller K, Kane J, Cannada M, Murtha K, Sims DW, Knapp KA, Kabala HA, Goins EL, Tafra L, Wareham J, Mullican L, Joseph J, Wells JM, Wolf NL, Kildee MM, Te J, Viollet C, Sukumar G, Bacikova D, Alba C, McGrath E, Polisetti S, Singh J, Adeleye A, Pollard H, Mitchell D, Gist G, Olowu V, Wilson KN, Conrads KA, Hood BL, Makohon-Moore S, Maxwell GL, Baldelli E, Nealeigh MD, Cutler ML, Russo M, Zimmer AS, Hanlon S, Proteogenomic characterization of invasive breast tumors in young women. NPJ Breast Cancer, 11(1):94(2025) [pubmed]

10.1038/s41523-025-00793-0;

submitter keyword: laser microdissection, proteogenomics,Breast cancer

Thomas P.
contact affiliation	Director of Women’s Health Research Women’s Service Line Inova Health System
contact email	conrads@whirc.org
lab head
Thomas Conrads
contact affiliation	Inova Health System
contact email	conrads@whirc.org
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/2025/08/PXD066224

PRIDE project URI

• PRIDE
  1. PXD066224
     1. Label: PRIDE project
     2. Name: Proteogenomic characterization of invasive breast tumors in young women