FIG. 1.

Tumor microenvironment is differentially regulated and exhibits cellular heterogeneity in young and aged ER-α⁺ breast cancer patients. (A) DAVID functional annotation tool was used to determine enriched pathways of tumors derived from young ER-α⁺ breast cancer patients. Genes with a fold change ≥1.3 were selected from TCGA data analyzed in this study. Findings show significant P values (*P < 0.05) for matrix, focal adhesion, cytokine, and PI3K/AKT pathways. (B) xCell cell type enrichment analysis of young (<45 years old) and aged (>65 years old) ER-α⁺ breast cancer patients revealed significant P values (*P < 0.05) for M2 macrophages, CD8⁺ T cells, and T_H2 cells. Both CD8⁺ T cells and T_H2 cells are enriched in young tumors, while M2 macrophages exhibit a lower quantity compared to aged. (C) Both adipocytes and MSCs exhibit similar quantities in young and aged ER-α⁺ breast tumors. AKT, protein kinase B; CM, conditioned medium; ER-α⁺, estrogen receptor-alpha positive; M1 Macs, M1 macrophage; M2 Macs, M2 macrophage; MSC, mesenchymal stem cell; PI3K, phosphoinositide 3-kinase; TCGA, The Cancer Genome Atlas; T_H2, T helper 2.