Figure 2.
Distant metastatic lesions in the TRAMP transgenic mouse model of prostate cancer exhibit stem cell–like expression signatures of the BMI-1 pathway. Transcripts differentially regulated in distant metastatic lesions of 6-month-old TRAMP mice (MTTS signature) were compared with the BMI-1–regulated genes in neural stem cells (3) in search of intersection of lists. (A) Expression profiles and the corresponding Pearson correlation coefficient for 199 genes (141 upregulated and 58 downregulated) comprising concordant differentially regulated sets of transcripts in metastatic TRAMP samples and PNS neurospheres are shown. Small gene expression signatures comprising transcripts with a high level of expression correlation in metastatic cancer cells and stem cells (the selection threshold for small signatures was arbitrarily set at Pearson correlation coefficients greater than 0.95) were selected from large concordant sets. The reduction in the signature transcript number was terminated when further elimination of a transcript did not increase the value of the Pearson correlation coefficient. Using this approach, a single candidate prognostic gene expression signature was selected for each binary intersection of the MTTS signature and parent stem cell signatures (Figure 3). Consecutive steps of selection from the 199-gene concordant set of a subset of 20 genes (A and B) and a small MTTS/PNS 11-gene signature (C and D) are shown. In D, r = 0.9897, P < 0.0001 between gene groups, and n = 11 per group. Complete lists of genes and corresponding concordant subsets are shown in Supplemental Table 2. See text, Figure 3, and Table 3 for details.