Extended Data Fig. 4: Additional analyses of MYC activity in prostate tumors and metastases.

a, Cross-species pathway analysis. Pathway-based GSEA comparing pathways enriched in the FHCRC human bone metastasis signature (Supplementary Table 6d) with those enriched in the mouse bulk RNA bone metastasis signature (Supplementary Table 6a). NES and p-values were estimated using 1,000 pathway permutations. b, Stouffer integration of the leading-edge pathways from the GSEA comparing the mouse (Supplementary Table 6a) and the two human bone metastases signatures (Supplementary Tables 6c,d) from panel a and Fig. 4b. The x-axis shows the Stouffer integrated NES. c, Bar graphs summarizing NES scores from GSEA of bone metastasis signatures from NPK^EYFP mice (Supplementary Table 2c), and the Balk and FHCRC human cohorts (Supplementary Tables 3c,d) showing enrichment of three independent MYC signatures: “Hallmarks” (human), “Dang” (human)²⁹ and “Sabo” (mouse)³⁰. NES and p-values were estimated using 1,000 gene permutations. d, Heatmap representation of single-sample GSEA enrichment of MYC activity based on enrichment of the Hallmarks MYC pathway in primary tumors from TCGA (n = 497) and metastases from SU2C (n = 270) (Supplementary Table 3). Gleason scores are shown for the primary tumors; metastases include all metastases in the SU2C cohort. Colors correspond to NES.