Fig. 5: Molecular and clinical correlates of ZNRF3 genomic loss. | Nature Communications

Fig. 5: Molecular and clinical correlates of ZNRF3 genomic loss.

From: Somatic driver mutation prevalence in 1844 prostate cancers identifies ZNRF3 loss as a predictor of metastatic relapse

Fig. 5: Molecular and clinical correlates of ZNRF3 genomic loss.

A Patients in the CPCG cohort ordered from left to right by percentage of the genome altered by a copy number aberration (PGA). Patient age at diagnosis (years) is also shown. Blue bars correspond with patients harboring ZNRF3 genomic loss. Heatmaps below show clinico-molecular features (ZNRF3 Loss, BCR at any time, BCR within 30 months of treatment, Metastasis, ETS Fusion status, and IDC-P/CA histology; ‘present’ in blue, ‘absent’ in white, ‘not available’ in gray), clinical prognostic factors (Gleason Score, pre-treatment PSA, and clinical T category), and treatment type (image-guided radiotherapy; IGRT, blue or radical prostatectomy; RP, orange); B Gene Set Enrichment Analysis of TCGA tumors harboring ZNRF3 loss. Colors represent q-value gradient. C Metastatic relapse-free rate in CPCG patients, stratified by ZNRF3 genomic loss and CCND1 genomic gain. p-value from a log-rank test (p = 7.48 × 10−23). Colors indicate different molecular profiles in each group. D Multivariable Cox Proportional Hazards analysis of metastatic relapse in CPCG patients, stratified by ZNRF3 genomic loss, CCP/Prolaris score (continuous), clinical prognostic factors, and PGA. p-values from a Wald test. Error bars represent 95% confidence intervals of the reported hazard ratios. E Volcano plot of genes upregulated in TCGA tumors harboring monoallelic ZNRF3 loss. Dashed line represents cutoff of statistical significance (q > 0.05). Colors show genes implicated in the DREAM (blue) or WNT (red) pathways, or both pathways (orange). F Significant RNA upregulation of genes implicated in polycomb repressive complex-1 and -2 (PRC2: EZH2, EED, SUZ12; PRC1: CBX2) in TCGA tumors (n = 493) harboring monoallelic losses of ZNRF3. *** p < 0.0001; ** p < 0.001. p-values from a Mann–Whitney U test. Centre of box represents the median value. Lower and upper box hinges correspond to the first and third quartile. Whiskers extend to the largest and smallest values no further than 1.5-times the Interquartile Range. Source data are provided as a Source Data file.

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