Fig. 3

Enrichment analyses indicate RARRES2 regulates lipid metabolic reprogramming and PI3K signaling pathway in breast cancer. a and b RARRES2 co-expression genes in TCGA-BRCA were analyzed for enrichment in Gene Ontology (GO) biological processes (a) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (b). The size of each bubble represents the number of genes, while the color represents the enrichment score. c and d GO biological process enrichment analysis of RARRES2 positive (c) or negative (d) co-expression genes in scRNA-seq of primary and BrM cancer epithelial cells mentioned in Fig. 1d. e Volcano plot showing the differentially expressed genes between RARRES2-OE and control MDA-MB-231 cells. Genes expressed at significantly higher levels in RARRES2-OE group are shown in red; genes expressed at significantly lower levels, blue; genes expressed non-significantly differently in the two cell lines, gray. The dashed lines indicate the cut-off in log₂ (FC) and log₁₀ (P-value) for a gene to be considered differentially expressed. f Gene set enrichment analysis of the differentially expressed genes between RARRES2-OE and control MDA-MB-231 cells showed upregulation of glycerophospholipid metabolism and biosynthesis of pantothenate and CoA, as well as downregulation of retinol metabolism and steroid hormone biosynthesis. g Differentially expressed genes in panel (e) were analyzed for enrichment in GO biological processes. The size of each bubble represents the number of genes in the process, while the color represents the -log₁₀ (P-value). RARRES2 retinoic acid receptor responder 2, PI3K phosphatidylinositol 3-kinase, FC fold change, BrM brain metastasis, scRNA-seq single-cell RNA-sequencing, RARRES2-OE RARRES2 overexpression, mTOR mammalian target of rapamycin, NES normalized enrichment score, FDR false discovery rate