Fig. 4: Aberrant methylation of ZNRF3 in aggressive localized prostate cancer.

A The ZNRF3 5’ promoter (probe cg11986861) is significantly hypermethylated in localized prostate cancers harboring low ZNRF3 RNA abundance. Coordinates refer to the GRCh37 (hg19) human genome build. Blue dots represent probes with statistically significant differential methylation (Q < 0.05). B ZNRF3 RNA abundance is inversely associated with methylation of the ZNRF3 5’ promoter. Shaded area shows 95% confidence interval of the best fit line. Two-sided p-value generated from a permutation test. C, D ZNRF3 5’ promoter methylation is significantly elevated in tumors harboring ZNRF3 allelic losses. p-values from a Mann–Whitney U test. CPCG: n = 286 patients; TCGA: n = 493 patients. 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. E, F Patients whose tumors harbor >1 aberrant ZNRF3-associated feature (i.e. monoallelic loss, low RNA abundance, 5′ promoter hypermethylation) are at significantly higher risk of metastatic relapse (E; CPCG) and disease progression (F; TCGA) than those patients with one or no features. p-values from a log-rank test. Colors indicate the number of features present in the tumor. Source data are provided as a Source Data file.