Fig. 5: Proteogenomic insights into the Basal subtype reveal enhanced neuroendocrine properties.

a Volcano plot showing differences in protein abundance between the Basal subtype and other subtypes (Student’s t-test). Representative KEGG pathways for > 2-fold upregulated and downregulated proteins are listed. b Bar plots showing representative enriched Reactome pathways using 138 significantly upregulated phosphoproteins in the Basal subtype. c Heatmap showing the abundance of phosphosites involved in the Reactome pathway Vesicle-mediated transport across the three proteomic subtypes. d Heatmaps showing the cis-effect of DNA methylation on cognate mRNA and protein abundance in four neurotransmitter conduction-related genes (NCAM1, VAMP4, CADM1, CALML3) in Basal tumors. Methylation level (β-value), mRNA abundance (FPKM) and protein abundances were displayed in this heatmap after normalization by row Z-score. e Scatter plot showing the correlation between the abundance of CAMK2B protein and CAMK2B T287 phosphosite. Pearson’s R and P-values are shown within the plot. f Differential mRNA and protein abundance of MTC-specific biomarkers and broad-spectrum neuroendocrine markers between the Basal subtype and other subtypes. P-values are calculated by Student’s t-test for global proteomic data, or calculated by DESeq2 based on the negative binomial distribution for RNA-Seq data. The right panel shows the –log₁₀-transformed P-values of the two omics (upper bar for proteomic data, lower bar for RNA-Seq data). g Heatmap showing the abundance of 67 candidate drug target proteins of the Basal subtype. See also Supplementary Table S9.