Fig. 1

RARRES2 is downregulated in breast cancer brain metastasis (BrM). a Heatmap showing transcription levels of 25 common adipokine-related genes in parental and MDA-MB-231 BrM cells (left), and in MDA-MB-231-BrM3 cells xenografted into mouse fatpad and skin or brain (right). Data came from the public datasets indicated at the bottom of the heatmaps. Blue indicates lower expression, while red indicates higher expression. b Comparison of RARRES2 expression between paired primary breast tumors (n = 22) and metastatic tumors to the brain (n = 22). ^****P < 0.0001 (paired-sample t test). c Immunohistochemistry staining for RARRES2 in formalin-fixed, paraffin-embedded sections from primary triple negative breast cancer (TNBC, upper row) or tumors that had metastasized to the brain (lower row) in our patient. The black boxes indicate the area shown at higher magnification (Scale bar = 10 μm) in the insets at the lower right of each micrograph (Scale bar = 100 μm). d scRNA-seq data analysis of RARRES2 expression from human TNBC (Primary) and BrM cancer epithelial cells, presented as tSNE plots. e RARRES2 expression in human breast tumor tissues (n = 16), brain tumor tissues (n = 16), and BCBrM tissues (n = 3). Data were from the public dataset GSE100534. ^**P = 0.0016, ^***P = 0.0003 (one-way ANOVA followed by Dunnett’s multiple-comparisons test). f RARRES2 expression in human breast cancer that had metastasized to lung (n = 4), bone (n = 10) or brain (n = 15). Data were from the public dataset GSE14020. ^*P = 0.019, ^***P < 0.001 (one-way ANOVA followed by Dunnett’s multiple-comparisons test). g RARRES2 expression in breast cancer cells before injection (n = 4) into mice and after metastasis to the liver (n = 6), lung (n = 6), or brain (n = 8). Data came from GSE148283. ^***P = 0.0003 (one-way ANOVA followed by Dunnett’s multiple-comparisons test). h RARRES2 expression in primary breast tumors (n = 3) and tumors that had metastasized to the lung (n = 3), bone (n = 3) or liver (n = 3) in mice. Data came from the public dataset GSE62598. The P-value was determined using one-way ANOVA. RARRES2 retinoic acid receptor responder 2, BCBrM breast cancer brain metastasis, scRNA-seq single-cell RNA-sequencing