Project 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.

2025-08-25 | PXD066224 | Pride

Homo sapiens whole blood.

Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.

2019-07-31 | GSE114179 | GEO

Homo sapiens

Project description:Gene expression profile of breast cancer cells.

| PRJNA192571 | ENA

Molecular mechanism of EPC1-PHF1 fusion protein (ChIP-seq Homo Sapiens)

Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.

2020-11-25 | GSE162118 | GEO

Homo sapiens immortalized MSCs: 3A6

Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.

2010-09-25 | GSE24338 | GEO

Homo sapiens

Project description:MSI2 gene expression profile in breast cancer cell

| PRJNA315268 | ENA