Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Samsung Genomic Institute, Samsung Biological Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Sci Rep. 2016 Jun 24;6:28623. doi: 10.1038/srep28623.
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.
乳腺癌脑转移（BCBM）的生物学特性尚未完全阐明。本研究旨在探索与原发性乳腺癌（BC）脑转移过程相关的基因。我们采用 NanoString nCounter 分析技术，对 20 例复发至脑的原发性 BC 和 41 例 BCBM 样本进行了 252 个靶基因表达水平的比较。在 BCBM 中，PAM50 固有亚型（如 HER2 富集型和基底样型）明显过表达。我们发现 22 个基因在原发性 BC 和 BCBM 之间存在明显差异表达。其中 5 个基因（CXCL12、MMP2、MMP11、VCAM1 和 MME），之前与肿瘤进展、血管生成和转移有关，可明确区分原发性 BC 和 BCBM。值得注意的是，与 BCBM 相比，这 5 个基因在原发性 BC 中明显上调。相反，SOX2 和 OLIG2 基因在 BCBM 中上调。这些基因可能参与转移定植，但不参与原发性肿瘤的发生。在患者匹配的配对样本（n=17）中，8 例（47.1%）观察到 PAM50 分子亚型转换，具有明显基因表达的患者亚型转换呈不利趋势。虽然我们的研究结果尚无定论，但揭示了可能介导脑转移过程的差异表达基因。
