Freitas Ana Julia Aguiar de, Varuzza Muriele Bertagna, Calfa Stéphanie, Causin Rhafaela Lima, Silva Vinicius Duval da, Souza Cristiano de Pádua, Marques Márcia Maria Chiquitelli
Molecular Oncology Research Center, Teaching and Research Institute, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil.
Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil.
Int J Mol Sci. 2025 Jul 19;26(14):6944. doi: 10.3390/ijms26146944.
Breast cancer is a leading cause of central nervous system (CNS) metastases in women, often associated with poor prognosis and limited therapeutic options. However, molecular differences between primary tumors and CNS metastases remain underexplored. We aimed to characterize transcriptomic differences between primary breast tumors and matched CNS metastases and identify immune-related biomarkers associated with metastatic progression and patient outcomes. Transcriptomic profiling was based on 11 matched FFPE sample pairs (primary tumor and CNS metastasis). Paired formalin-fixed paraffin-embedded (FFPE) samples from primary tumors (T1) and CNS metastases (T2) were analyzed using the NanoString nCounter platform and the PanCancer IO 360™ Gene Expression Panel. Differential gene expression, Z-score transformation, and heatmap visualization were performed in R. In silico survival analyses for overall survival (OS) and recurrence-free survival (RFS) were conducted using publicly available TCGA and GEO datasets. Forty-five genes were significantly differentially expressed between the T1 and T2 samples. Immune-related genes such as CXCL9, IL7R, CD79A, and CTSW showed consistent downregulation in CNS metastases. High expression of CXCL9 and CD79A was associated with improved OS and RFS, whereas high IL7R and CTSW expression correlated with worse outcomes. These findings indicate immune suppression as a hallmark of CNS colonization. Comparative transcriptomic analysis further underscored the distinct molecular landscapes between primary and metastatic tumors. This study highlights transcriptional signatures associated with breast cancer CNS metastases, emphasizing the role of immune modulation in metastatic progression. The identified genes have potential as prognostic biomarkers and therapeutic targets, supporting the need for site-specific molecular profiling in metastatic breast cancer management.
乳腺癌是女性中枢神经系统（CNS）转移的主要原因，常与预后不良和治疗选择有限相关。然而，原发性肿瘤与CNS转移之间的分子差异仍未得到充分探索。我们旨在表征原发性乳腺肿瘤与匹配的CNS转移之间的转录组差异，并确定与转移进展和患者预后相关的免疫相关生物标志物。转录组分析基于11对匹配的福尔马林固定石蜡包埋（FFPE）样本对（原发性肿瘤和CNS转移）。使用NanoString nCounter平台和泛癌IO 360™基因表达面板分析来自原发性肿瘤（T1）和CNS转移（T2）的配对福尔马林固定石蜡包埋（FFPE）样本。在R中进行差异基因表达、Z分数转换和热图可视化。使用公开可用的TCGA和GEO数据集进行总生存期（OS）和无复发生存期（RFS）的计算机生存分析。T1和T2样本之间有45个基因存在显著差异表达。CXCL9、IL7R、CD79A和CTSW等免疫相关基因在CNS转移中表现出一致的下调。CXCL9和CD79A的高表达与OS和RFS的改善相关，而IL7R和CTSW的高表达与较差的预后相关。这些发现表明免疫抑制是CNS定植的一个标志。比较转录组分析进一步强调了原发性肿瘤和转移性肿瘤之间不同的分子格局。本研究突出了与乳腺癌CNS转移相关的转录特征，强调了免疫调节在转移进展中的作用。所鉴定的基因有潜力作为预后生物标志物和治疗靶点，支持在转移性乳腺癌管理中进行位点特异性分子分析的必要性。
