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.
Highlights
Brain metastasis (BM) remains an intractable clinical problem despite notable advances in the treatment of breast cancer (BC)
NanoString nCounter in surgically resected breast cancer brain metastasis (BCBM) and primary BC relapsing to brain, we aimed to investigate molecules associated with the brain metastasis processes
The frequency of diagnosis of BCBM seems to be increasing as a result of improved imaging modalities and longer survival due to effective systemic control of the primary BC
Summary
Brain metastasis (BM) remains an intractable clinical problem despite notable advances in the treatment of breast cancer (BC). The prevalence of breast cancer brain metastasis (BCBM) has been reported to range from 10–30%1,2. Many genes showing increased expression that correlates with brain metastasis have been identified, and some have been shown to play a causal role in this process[6]. Gene expression analysis between brain metastatic and parental breast cancer cell lines performed by Bos et al indicated that HBEGF, COX2, and ST6GALNAC5 mediate brain metastasis[7]. Despite advances in our knowledge of the genetic basis for cancer metastasis, comprehensive genomic characterization of BCBM for development of biomarkers and molecularly targeted therapies remains an unmet need. NanoString nCounter in surgically resected BCBM and primary BC relapsing to brain, we aimed to investigate molecules associated with the brain metastasis processes
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