Fig. 1: A specific landscape of alternative RNA splicing linked to TNBC metabolic dysregulation.

a Workflow of the analytical process performed in this study. b Volcano plots illustrating the protein profiles of 2147 proteins displaying abnormal protein levels in TNBC (|log₂-fold changes|>1, Benjamini‒Hochberg adjusted P < 0.01). A comprehensive set of 372 RNA-related proteins spanning various functional categories was meticulously color-coded for individual representation. c Landscape of AS for TCGA samples (n = 1096), as determined by splicing event PSI scores (on the left) and the expression levels of 109 core spliceosome genes (on the right). Each point corresponds to an individual sample, with color coding denoting their sample types, including normal tissues, non-TNBC, and MPSs. The position of each sample is computed as a t-SNE representation of the higher-dimensional splice event PSI matrix and expression matrix. d Top: global differences in spliceosome gene expression between basal, non-basal, and normal tissues in the FUSCC-TNBC cohort (n = 360). The distribution distances (r.m.s.d.) were calculated between basal tumors and corresponding normal tissues (red), non-basal tumors and corresponding normal tissues (green), and different samples of normal tissues (navy). Bottom: global differences in spliceosome gene expression between MPS subtypes in the FUSCC-TNBC cohort. The distribution distances (r.m.s.d.) were calculated between MPS1 (blue), MPS2 (red), and MPS3 (yellow) tumors and their corresponding normal tissues. P values were obtained from the two-sided Wilcoxon rank-sum test and the two-sided Kruskal–Wallis test (***P < 0.001). The centerline indicates the median, and the bounds of the box indicate the 25th and 75th percentiles. e Heatmap displaying normalized expression levels of 42 core spliceosome genes upregulated in tumors for each individual sample in the FUSCC-TNBC cohort. The sample types, four TNBC transcriptomic subtypes, and three TNBC metabolic subtypes were annotated. f Volcano plot of the 594 annotated metabolites between MPS1 and MPS2. Significantly differentially abundant metabolites are colored blue for upregulated MPS1 and red for upregulated MPS2. g mRNA expression of GAPDH, GSR, GSS, LDHA, LDHB, PFKM, PFKP, and UGP2 in the three MPS subtypes in the FUSCC-TNBC cohort (Wilcoxon test). The centerline indicates the median, and the bounds of the box indicate the 25th and 75th percentiles. IM immunomodulatory subtype, LAR luminal androgen receptor, BLIS basal-like immune-suppressed subtype, MES mesenchymal-like subtype, AMP adenosine monophosphate, F-1,6-BP fructose 1,6-diphosphate, NAD nicotinamide adenine dinucleotide, SAM S-adenosylmethionine, 3’,5’-ADP adenosine 3’,5’-diphosphate.