Importantly, OPRK1 protein levels positively correlated with the NE marker NSE in CRPC samples (Fig. 1J, K), and OPRK1 mRNA expression showed strong correlations with NE biomarkers (NCAM2 and CGA) across five independent prostate cancer cohorts (SU2/PCF Dream Team, 2019 [25], SU2/PCF Dream Team, 2015 [26], MSK, 2010 [27], Fred Hutchinson CRC 2016 [28] and MSK 2022) (Supplementary Fig. 1D). This evidence concerns the gene ENO2 and prostate cancer.