Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA167135 | ENA |
REPOSITORIES: ENA
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Project description:Brain metastases from breast and other cancers constitute an important part of therapeutic failures and are associated with severe morbidity and mortality. Here, we have examined histopathological data and generated gene expression data in two independent cohorts of primary tumors from HER2-positive advanced breast cancer patients. We report that the combination of estrogen receptor (ER) negativity and expression of a novel 13-gene signature identify a subset of patients with rapid (median, 31 and 41 months in discovery and validation cohorts, respectively) versus slower (median, 66 months and 77 months in discovery and validation cohorts, respectively) development of brain metastases (P<0.0001). The 13-gene signature also predicted rapid brain metastasis formation within the ER-negative subset of patients (P=0.014). Interestingly, three of the genes in the signature (RAD51, BARD1, FANCG) function in DNA double strand break repair. Overexpression of RAD51 in immortal MCF-10A breast epithelial cells altered their three-dimensional acinar morphology to increase the percentage of invasive structures by 6.5 fold, in the presence or absence of HER2 overexpression. In summary, ER negativity and a novel 13-gene signature may have the potential to identify subpopulations at highest immediate risk for the development of brain metastases in HER2-positive advanced breast cancer. Our results also suggest that RAD51, found in the 13-gene signature, may promote aggressiveness in breast epithelial cells. These data may be useful in the design of brain metastasis preventive trials and may prompt new treatment strategies Median normalized data provided
2012-07-01 | GSE38057 | GEO
Project description:Molecular Signature of Pregnancy Associated Breast Cancer (PABC)
2025-01-24 | E-GEOD-31192 | ExpressionAtlas
Project description:Purpose: There is an unmet clinical need for biomarkers to identify breast cancer patients who are at increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with HER2+ brain metastasis. Experimental Design: Gene expression of 19 HER2+ breast cancer brain metastases was compared with HER2+ nonmetastatic primary tumors. Gene Set Enrichment Analysis was used to identify a signature, which was evaluated for correlation with BRCA1 mutation status and clinical outcome using published microarray datasets and for correlation with pharmacological inhibition by a PARP inhibitor and temozolomide using published microarray datasets of breast cancer cell lines. Results: A BRCA1 Deficient-Like (BD-L) gene signature is significantly correlated with HER2+ metastases in both our and an independent cohort. BD-L signature is enriched in BRCA1 mutation carrier primary tumors and HER2-/ER- sporadic tumors, but high values are found in a subset of ER+ and HER2+ tumors. Elevated BD-L signature in primary tumors is associated with increased risk of overall relapse, brain relapse, and decreased survival. The BD-L signature correlates with pharmacologic response to PARP inhibitor and temozolomide in two independent microarray datasets, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. Conclusions: The BD-L signature is enriched in breast cancer brain metastases and identifies a subset of primary tumors with increased propensity for brain metastasis. Furthermore, this signature may serve as a biomarker to identify sporadic breast cancer patients who could benefit from a therapeutic combination of PARP inhibitor and temozolomide. Gene expression of 19 HER2+ human breast cancer brain metastases was compared with gene expression of 19 HER2+ nonmetastatic primary human breast tumors.
2014-04-24 | E-GEOD-43837 | biostudies-arrayexpress
Project description:Pivotal role of HMGA1 gene signature in highly metastatic breast cancer
2025-01-24 | E-GEOD-35525 | ExpressionAtlas
Project description:A BRCA1 Deficient-Like Signature is Enriched in Breast Cancer Brain Metastases
| PRJNA187530 | ENA
Project description:Breast cancer in young patients is known to exhibit more aggressive biological behavior and is associated with a less favorable prognosis than the same disease in older patients, owing in part to an increased incidence of brain metastases, the mechanistic explanations behind which remain poorly understood. We recently reported that young mice, compared to older mice, showed about a three-fold increase in the development of brain metastases in mouse models of triple-negative and luminal B breast cancer. Here we have performed a quantitative mass spectrometry-based proteomic analysis to identify proteins contributing to age-related disparities in the development of breast cancer brain metastases. Using a mouse model of brain-tropic (MDA-MB-231BR) triple-negative breast cancer, we harvested subpopulations of tumor metastases, the tumor-adjacent metastatic microenvironment, and uninvolved brain tissues via laser microdissection followed by quantitative proteomic analysis using high resolution mass spectrometry to characterize differentially abundant proteins contributing to age-dependent rates of brain metastasis.
2024-01-11 | PXD042346 | Pride
Project description:Development of Transcriptomic Biomarker Signature in Human Saliva to Detect Lung Cancer
2025-01-24 | E-GEOD-32175 | ExpressionAtlas
Project description:Purpose: There is an unmet clinical need for biomarkers to identify breast cancer patients who are at increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with HER2+ brain metastasis. Experimental Design: Gene expression of 19 HER2+ breast cancer brain metastases was compared with HER2+ nonmetastatic primary tumors. Gene Set Enrichment Analysis was used to identify a signature, which was evaluated for correlation with BRCA1 mutation status and clinical outcome using published microarray datasets and for correlation with pharmacological inhibition by a PARP inhibitor and temozolomide using published microarray datasets of breast cancer cell lines. Results: A BRCA1 Deficient-Like (BD-L) gene signature is significantly correlated with HER2+ metastases in both our and an independent cohort. BD-L signature is enriched in BRCA1 mutation carrier primary tumors and HER2-/ER- sporadic tumors, but high values are found in a subset of ER+ and HER2+ tumors. Elevated BD-L signature in primary tumors is associated with increased risk of overall relapse, brain relapse, and decreased survival. The BD-L signature correlates with pharmacologic response to PARP inhibitor and temozolomide in two independent microarray datasets, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. Conclusions: The BD-L signature is enriched in breast cancer brain metastases and identifies a subset of primary tumors with increased propensity for brain metastasis. Furthermore, this signature may serve as a biomarker to identify sporadic breast cancer patients who could benefit from a therapeutic combination of PARP inhibitor and temozolomide.
2014-04-24 | GSE43837 | GEO
Project description:A six-gene signature predicting breast cancer lung metastasis
| PRJNA107071 | ENA