Genomic Profiling of Brain Metastasis and Matched Primary Triple-negative Breast Cancer

AbstractBrian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood–brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.

Download Full-text

Distinct MR Imaging Features of Triple-Negative Breast Cancer with Brain Metastasis

Journal of Neuroimaging ◽

10.1111/jon.12149 ◽

2014 ◽

Vol 25 (3) ◽

pp. 474-481 ◽

Cited By ~ 10

Author(s):

Ren-Hua Yeh ◽

Jyh-Cherng Yu ◽

Chi-Hong Chu ◽

Ching-Liang Ho ◽

Hung-Wen Kao ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastasis ◽

Mr Imaging ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Imaging Features

Download Full-text

Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20123080 ◽

2019 ◽

Vol 20 (12) ◽

pp. 3080 ◽

Cited By ~ 4

Author(s):

Fan Wu ◽

Robert D. McCuaig ◽

Christopher R. Sutton ◽

Abel H. Y. Tan ◽

Yoshni Jeelall ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastasis ◽

Cancer Progression ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Lung Metastases ◽

Her2 Positive ◽

Pathway Gene ◽

Dual Specificity ◽

The Brain

DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations. All TNBC patients contained HER2-positive CTCs. HER2-positive CTCs were associated with increased ERK1/ERK2 expression, which are direct DUSP6 targets. DUSP6 protein expression was predominantly nuclear in breast CTCs and the brain metastases but not pleura or lung metastases of TNBC patients. Therefore, nuclear DUSP6 may play a role in the association with cancer spreading in TNBC patients, including brain metastasis.

Download Full-text