Immune response pathways enriched in breast cancer samples with brain metastasis

Abstract

Background: Breast cancer (BC) is the most common form of cancer in women. BC brain metastasis (BM) is associated with poor prognosis, especially for Triple negative breast cancer (TNBC). However, the driver genes of this clinical characteristic are poorly understood. Methods: This study conducted a transcriptome-wide analysis of gene expression levels in BCBM samples from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. Clinical data and gene expression matrix of TNBC samples were collected. Differential analysis and functional enrichment of metastasis vs. non metastasis data samples were conducted. Genes associated with overall survival and BM event was scanned. Results: Up-regulation in 120 genes and down-regulation in 56 genes were found in TNBC metastasis data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) clustering using expression alternated genes showed unique immune-gene enrichment in BM samples. Immune response category GO:000695 was found as the most significant term associated with metastasis event. KEGG pathways including cytokine pathways and Primary immunodeficiency were significantly changed in metastasis samples. ESR1 and FYB2 genes expression changes were found to be linked to survival or BM events. Conclusions: Our results suggest that data-mining on the immune microenvironment of BM might be useful in future study.