The expression of YWHAZ and NDRG1 predicts aggressive outcome in human prostate cancer

Some prostate cancers (PCas) are histo-pathologically grouped within the same Gleason Grade (GG), but can differ significantly in outcome. Herein, we aimed at identifying molecular biomarkers that could improve risk prediction in PCa. LC ESI-MS/MS was performed on human PCa and benign prostatic hyperplasia (BPH) tissues and peptide data was integrated with omic analyses. We identified high YWHAZ and NDRG1 expression to be associated with poor PCa prognosis considering all Gleason scores (GS). YWHAZ and NDRG1 defined two subpopulations of PCa patients with high and intermediate risk of death. Multivariable analyses confirmed their independence from GS. ROC analysis unveiled that YWHAZ outperformed GS beyond 60 months post-diagnosis. The genomic analysis of PCa patients with YWHAZ amplification, or increased mRNA or protein levels, revealed significant alterations in key DNA repair genes. We hereby state the relevance of YWHAZ in PCa, showcasing its role as an independent strong predictor of aggressiveness. Using integrative tissue-omics, Lage-Vickers, Bizzotto et al. classify prostate cancer patients into high YWHAZ and NDRG1 expression subgroups that correlate with a high and intermediate risk of disease progression. This study identifies molecular biomarkers associated with aggressive prostate cancer.

Automated summary

This study identifies high YWHAZ and NDRG1 expression as molecular biomarkers associated with poor prognosis in prostate cancer patients, defining two subgroups with high and intermediate risk of disease progression. YWHAZ outperforms Gleason score in predicting aggressiveness of prostate cancer beyond 60 months post-diagnosis.