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. 2025 Jul 19;26(14):6944.
doi: 10.3390/ijms26146944.

Transcriptomic Profiling of Paired Primary Tumors and CNS Metastases in Breast Cancer Reveals Immune Modulation Signatures

Ana Julia Aguiar de Freitas  1 , Muriele Bertagna Varuzza  1 , Stéphanie Calfa  1 , Rhafaela Lima Causin  1 , Vinicius Duval da Silva  2 , Cristiano de Pádua Souza  2 , Márcia Maria Chiquitelli Marques  1
Affiliations

Transcriptomic Profiling of Paired Primary Tumors and CNS Metastases in Breast Cancer Reveals Immune Modulation Signatures

Ana Julia Aguiar de Freitas et al. Int J Mol Sci. .

Abstract

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.

Keywords: CNS metastases; NanoString; breast cancer; gene expression; immune biomarkers; personalized oncology.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Heatmap representing differential gene expression between primary tumors (T1) and CNS metastases (T2).
Figure 2
Figure 2
In silico analysis of (A) overall survival and (B) recurrence-free survival.
Figure 3
Figure 3
Gene expression comparison: primary tumor (T1) vs. metastasis (T2).
See this image and copyright information in PMC

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