Characterization of the tumor microenvironment in breast cancer brain metastasis.

Objective: The difference in the tumor microenvironment (TME) between primary breast cancer (PBC) and breast cancer brain metastasis (BCBM) is still unknown. Herein, we present the landscape of the TME in PBC and BCBM to better understand the process of BCBM.

Methods: The Gene Expression Omnibus (GEO) database was used to obtain suitable PBC and BCBM data. Hub genes that were differentially expressed between the two groups were searched. Gene Ontology (GO) and KEGG were used to define the gene's function. Single-cell data were also analyzed to determine the difference between PBC and BCBM.

Results: Two datasets (GSE100534 and GSE125989) were used to search for hub genes, and 79 genes were either upregulated or downregulated between the two groups. Four hub genes (COL1A1, PDGFR, MMP3 and FZD7) were related to prognosis. GO and KEGG analyses showed that extracellular matrix and focal adhesion play major roles in the metastasis process. Another two datasets (GSE176078 and GSE186344) were enrolled for single-cell analysis. Single-cell analysis demonstrated that immune cells (66.6 %) form the main part of PBC, while cancer-associated fibroblasts (CAFs) (21.7 %) are the main component of BCBM. Immune cell proportion analysis showed that CD4+/CD8+ T cells (28.9 % and 14.3 %, respectively) and macrophages(M2) accounted for the majority of cells in PBC and BCBM, respectively. Further analysis of the classification of CAFs showed that apCAFs were significantly higher in PBC.

Conclusions: This study presents the landscape of BCBM with hub gene searching and single-cell analysis. Showing the difference in the tumor/immune microenvironment of PBC and BCBM, would be beneficial to explore immunotherapy and targeted therapy for BCBM.