Extended Data Fig. 7: Additional analyses of discovery of a MYC-correlated signature in prostate cancer metastasis.
a,b, GSEA using the PROMOTE-559 gene signature (Supplementary Table 8) to query the bone metastasis gene signature from the NPKEYFP mice (Supplementary Table 2c) (in a) and the human bone metastasis gene signature (Supplementary Table 3c) (in b); NESs and p-values were estimated using 1,000 gene permutations. c, Association with adverse outcome for metastasis. Each of the META-55 genes was evaluated by univariable Cox proportional hazards analysis for time-to-metastasis outcome in the TCGA dataset (n = 336 with available time to follow-up, Supplementary Table 3) and ranked by the strength of the association (that is, Wald test p-value), with a cutoff at p-value<10–7 from Wald test used to identify the 16 top-genes constituting the META-16 gene signature (Supplementary Table 8). d, Random model. To evaluate the probability that not any random group of 16 genes would be upregulated in the SU2C (n = 270) versus the TCGA (n = 497) cohorts, we constructed a null model using 10,000 iterations, with the x-axis showing -log2 p-value (from the two-sample one-tailed Welch t-test) between TCGA and SU2C comparisons and y-axis showing its probability density. The p-value of this random model thus represents an estimate of the number of times two-sample one-tailed Welch t-test p-values for a random 16 genes reached or outperformed two-sample one-tailed Welch t-test p-values for the META-16 genes. The p-value for the analogous random model for META-55 was P = 0.036.
