Heterocellular gene signatures reveal luminal-A breast cancer heterogeneity and differential therapeutic responses

Association of breast cancer with heterocellular subtypes. a Heatmap showing the expression of the top highly variable genes (standard deviation; SD >？2), specifically immune genes, and their association with breast cancer subtype samples (n？=？817) from TCGA.23 Highlighted genes represent selected immune specific genes that show high expression in multiple subtypes. b Proportion of CMS subtypes in multiple breast cancer data sets–TCGA23 (n？=？671) and {"type":"entrez-geo","attrs":{"text":"GSE42568","term_id":"42568"}}GSE4256824 (n？=？69). c Proportion of heterocellular subtypes in multiple breast cancer data sets–TCGA23 (n？=？407) and {"type":"entrez-geo","attrs":{"text":"GSE42568","term_id":"42568"}}GSE4256824 (n？=？63). Although heterocellular signatures were derived from entirely different cancer type (CRC), we observed that about half of the breast cancer samples were classified into all of the five heterocellular subtypes (stringent cutoff was used for mixed/low-confidence sample selection as discussed;13 Supplementary Table 1c). d Heatmap showing sample enrichment analysis using hypergeometric test-based FDR values comparing heterocellular subtypes (y axis) with intrinsic gene expression subtypes (x axis) in the TCGA23 breast cancer data set (n？=？407; Supplementary Table 1e–g). e Pie chart showing proportions of different heterocellular subtypes in luminal-A breast cancer samples (total n？=？202; enterocyte (n？=？31), goblet-like (n？=？34), inflammatory (n？=？25), stem-like (n？=？90), TA (n？=？22); TCGA breast cancer23). Only those samples classified into subtypes with high confidence by the CMS and heterocellular classifiers were shown in b–e). Summary of low and high confidence samples for both subtype classifications are shown in Supplementary Tables 1a–d and 2a–d and described in Methods sectio