Fig. 3: Coexistence of hormone-sensitive and -resistant pathways in the epithelium of fibroadenomas.

a KEGG analysis of differentially expressed genes in epithelial cells between fibroadenoma and normal tissue. Pathway analysis was determined by a hypergeometric test, one-sided and adjusted p < 0.05 was considered statistically significant. b GSEA of the estrogen signaling pathway and endocrine resistance pathway in epithelial cells between fibroadenoma and normal tissue. c Heatmap of the average expression of endocrine resistance genes from (b) in epithelial cells. d The expression of endocrine resistance genes (ERBB2, BCL2, and CCND1) in relapsed and non-relapsed fibroadenoma patients using immunohistochemical staining. Data are expressed as the mean +/− s.e.m. Each dot represents one patient. *p = 0.01306 (ERBB2, non-relapse: n = 9; relapse: n = 15), two-sided, Fisher’s test. ***p = 0.0006 (BCL2, non-relapse: n = 9; relapse: n = 15), *p = 0.0142 (CCND1, non-relapse: n = 7; relapse: n = 15), unpaired two-tailed Student’s t test. e The expression of endocrine resistance genes (ERBB2, BCL2, and CCND1) in breast cancer patients who had been pathologically proven to be derived from fibroadenoma by immunohistochemical staining. Data are expressed as the mean +/− s.e.m. Each dot represents one patient. **p = 0.00699 (ERBB2, breast cancer: n = 8; fibroadenoma: n = 8), two-sided Fisher’s test. **p = 0.0054 (BCL2, breast cancer: n = 8; fibroadenoma: n = 8), **p = 0.0027 (CCND1, breast cancer: n = 8; fibroadenoma: n = 8), paired two-tailed t test. f Immunohistochemical staining of hormone-sensitive and hormone-resistant markers in different patients. Scale bar: 50 μm. Experiment was performed with three independent replicates. g Heatmap of log-normalized expression (log2(count + 1)) of hormone-sensitive and resistance genes in epithelial cells between fibroadenoma and normal tissue. h Phenotypic distribution of epithelial cells (hormone sensitive, endocrine resistant, both sensitive and resistant, unrelated). i Relative proportion of endocrine-resistant epithelial cell subsets in each patient. Source data are provided as a Source data file.