Related Experiment Video
Updated: Mar 19, 2026
Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells
Published on: February 4, 2021
Gene Expression Profiling of Breast Cancer Brain Metastasis
Ji Yun Lee1, Kyunghee Park2, Eunjin Lee2
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Abstract:
The biology of breast cancer brain metastasis (BCBM) is poorly understood. We aimed to explore genes that are implicated in the process of brain metastasis of primary breast cancer (BC). NanoString nCounter Analysis covering 252 target genes was used for comparison of gene expression levels between 20 primary BCs that relapsed to brain and 41 BCBM samples. PAM50-based intrinsic subtypes such as HER2-enriched and basal-like were clearly over-represented in BCBM. A panel of 22 genes was found to be significantly differentially expressed between primary BC and BCBM. Five of these genes, CXCL12, MMP2, MMP11, VCAM1, and MME, which have previously been associated with tumor progression, angiogenesis, and metastasis, clearly discriminated between primary BC and BCBM. Notably, the five genes were significantly upregulated in primary BC compared to BCBM. Conversely, SOX2 and OLIG2 genes were upregulated in BCBM. These genes may participate in metastatic colonization but not in primary tumor development. Among patient-matched paired samples (n = 17), a PAM50 molecular subtype conversion was observed in eight cases (47.1%), with a trend toward unfavorable subtypes in patients with the distinct gene expression. Our findings, although not conclusive, reveal differentially expressed genes that might mediate the brain metastasis process.
Insights
Researchers identified key genes involved in breast cancer brain metastasis (BCBM). Specific genes like CXCL12 and MMP2 were upregulated in primary tumors, while SOX2 and OLIG2 were higher in BCBM, potentially aiding colonization.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer brain metastasis (BCBM) is a significant clinical challenge with poorly understood underlying biology.
- Identifying genes driving BCBM is crucial for developing targeted therapies and improving patient outcomes.
Purpose of the Study:
- To investigate gene expression differences between primary breast cancer (BC) and matched brain metastatic samples.
- To identify candidate genes that play a role in the process of brain metastasis.
Main Methods:
- NanoString nCounter Analysis was performed on 20 primary BCs and 41 BCBM samples, analyzing 252 target genes.
- Differential gene expression analysis was conducted to compare primary BC and BCBM samples.
- PAM50 intrinsic subtypes were assessed for their representation in BCBM.
Main Results:
- HER2-enriched and basal-like PAM50 subtypes were over-represented in BCBM.
- A panel of 22 genes showed significant differential expression between primary BC and BCBM.
- Five genes (CXCL12, MMP2, MMP11, VCAM1, MME) were upregulated in primary BC, while SOX2 and OLIG2 were upregulated in BCBM, suggesting roles in metastasis or colonization.
Conclusions:
- Differential gene expression patterns distinguish primary breast cancer from its brain metastases.
- Specific genes like SOX2 and OLIG2 may be critical for metastatic colonization in the brain.
- Further research is needed to validate these findings and explore their therapeutic potential in BCBM.
