Immune microenvironment heterogeneity and prognostic features prediction of breast cancer brain metastasis:a single-cell transcriptomics analysis

YANG Jun; LIU Dongyuan; ZHANG Dongxu; LIN Da; ZHANG Hongbing; WANG Hao

doi:10.3969/j.issn.1671-2897.2025.06.009

Abstract：Objective To reveal the differences between brain metastases and primary tumors at the cellular and molecular levels,with a focus on the immune microenvironment and genomic alterations,and develop a prediction model for patient prognosis.Methods Single-cell RNA sequencing was employed to analyze tumor samples.Doublet cells were identified using Scrublet,and data integration was performed with Scanpy.Highly variable genes were filtered,and batch effects were corrected using the Harmony algorithm.Differential gene expression was analyzed with the Wilcoxon rank-sum test,while copy number variations(CNVs)were inferred using infercnvpy.Prognostic models were developed using univariate Cox regression,LASSO regression,and multivariate Cox regression analyses.Results The study found that brain metastases exhibited a higher proportion of tumor cells and fewer immune cells compared to primary tumors,indicating an immunosuppressive microenvironment.Myeloid cells were predominantly lipid-metabolizing macrophages,with a significant reduction in dendritic cells,suggesting impaired antigen presentation.Natural killer(NK)cells and T cells were scarce,which further supported the immunosuppressive nature of brain metastases.CNV analysis revealed increased genomic alterations in brain metastases,which were associated with cell cycle dysregulation.Genes such as PLTP,CP,and ADGRG6 were identified as significantly associated with patient survival,suggesting their potential as prognostic biomarkers.Conclusions This study highlights the unique immunosuppressive environment and genomic complexity of brain metastases.The developed prognostic model shows potential for clinical application.Future therapeutic research should focus on targeting these pathways to improve the prognosis of patients with brain metastases.