Figure 3. Derived prognostic signatures in the context of prostate cancer multifocality with extreme grade differences.

(A) Our cohort included 8 informative multifocal cases (MF cases 1–8) with “extreme” grade differences (e.g., at least 1 low-grade [GG1] focus and at least 1 spatially independent high-grade [≥GG4] focus), as shown in the diagram on top. An integrative heatmap summarizes mxRNAseq profiling data supporting multifocality of these cases below. Individual T2:ERG fusion isoform expression and SPOP mutation status are shown for the 35 samples from these cases (case and GG of each sample shown according to the legend). T2:ERG/SPOP status (and unique T2:ERG isoform expression) support multifocality in these cases as described in the text). (B) Histology and mxRNAseq support extreme multifocality in case MF1, which had a large pT3a GG5 index tumor focus (orange). The posterior capsule section additionally contained a small, nearby but spatially distinct GG1 focus (green). Two samples were taken from the GG5 index focus (cyan 1 and 2), and 1 sample was taken from the GG1 focus (green, 3). Sample name, profiled morphologic GG, and SPOP mutation status is shown, along with high- and low-power histopathology of the indicated samples (original magnification, ×10 [top]; ×4 [bottom]). The morphology and SPOP p.F133V mutation only in the GG1 focus support clear multifocality. (C) Derived prognostic scores (mxCCP, mxGPS, mxGC), as well as expression levels of candidate prognostic long noncoding RNA (lncRNA) biomarkers (SCHLAP1 and PRCAT104) from MF 1 samples, are indicated as red points (stratified by profiled GG) overlying the distribution of all 125 localized prostate cancer samples from our cohort (see Figure 2A).