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Additional file 2. Fig. S1. Tumor/NAT differences. A Consensus clustering of samples (n = 81, K = 4) using the top 25% most variable proteins (n = 1,193, K = 4). B Differentially abundant protein-coding RNAs in tumors and NATs from The Cancer Genome Atlas (TCGA). Statistically significant genes (FDR < 0.05) are colored in black. C Associations of protein abundance changes between tumor versus NAT, and mpMRI-visible NAT versus mpMRI-invisible NAT. Only proteins that were significantly differentially expressed in tumor and NAT regions (FDR < 0.05) were used for this analysis. D Associations of protein-coding RNA abundance changes between tumor versus NAT, and mpMRI-visible tumor versus mpMRI-invisible tumor. Only protein-coding RNAs that were significantly differentially expressed in tumor and NAT regions (FDR < 0.05) were used for this analysis. Proteins or transcripts that were significant (FDR < 0.05) in the tumor-NAT comparison and had the same directionality are marked in black. NAT: histologically normal prostate adjacent to the tumor; mpMRI: multiparametric magnetic resonance imaging; FDR: Benjamini-Hochberg-adjusted p-value.

Additional file 1 Methods. Method details.

Multiparametric magnetic resonance imaging (mpMRI) has transformed management of localized prostate cancer by improving identification of clinically significant disease at diagnosis. Approximately 20% of primary prostate tumours are invisible to mpMRI, and we hypothesize that this invisibility reflects fundamental molecular properties of the tumour. We therefore profiled the genomes and transcriptomes of 40 ISUP Grade 2 tumors: 20 mpMRI invisible (PI-RADSv2 < 3) and 20 mpMRI visible (PI-RADSv2 5). mpMRI visible tumours were enriched for hallmarks of nimbosus, an aggressive pathological, molecular and microenvironmental phenomenon in prostate cancer. These hallmarks included more genomes with more somatic mutations, increased prevalence of IDC/CA pathology and altered abundance of 102 transcripts, including overexpression of non-coding RNAs like SCHLAP1. Multiple snoRNAs were identified, and a snoRNA signature synergized with nimbosus hallmarks to discriminate visible from invisible tumours. These data suggest a confluence of aggressive molecular and microenvironmental phenomena underlie mpMRI visibility of localized prostate cancer.