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

Sofia Lage-Vickers,Sergio Nemirovsky,Elba Vazquez,Carlos Scorticati,Maria Pia Valacco,Javier Cotignola,Geraldine Gueron,Estefania Labanca,Antonina Mitrofanova,Pablo Sanchis,Nora Navone,Osvaldo Mazza,Juan Bizzotto

doi:10.1038/s42003-020-01645-2

Abstract

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.

Highlights

Some prostate cancers (PCas) are histo-pathologically grouped within the same Gleason Grade (GG), but can differ significantly in outcome
We selected proteins enriched in PCa samples compared with benign prostatic hyperplasia (BPH) samples (PCa enriched protein data set, n = 109) (Fig. 1a)
In this work, we are reporting the relevance of YWHAZ/14-3-3ζ/δ as an independent strong predictor of death in PCa

Summary

Introduction

Some prostate cancers (PCas) are histo-pathologically grouped within the same Gleason Grade (GG), but can differ significantly in outcome. Because of tumor heterogeneity that is inadequately captured by the biopsies, between 25 and 50% of biopsies with certain GG come from men with higher-grade PCa4–6 This is known as “upgrading” between biopsy and prostatectomy, indicating that patients diagnosed with indolent PCa might have higher-grade and subsequently higher-risk cancers. The objective of our study was to identify novel biomarkers for risk stratification of PCa with an eye toward those that could behave independently from GS and further recognize intermediate GSs that may be more likely to progress These molecular biomarkers might improve the prediction of lethal disease and provide insight into the biological mechanisms underlying the strong relation of GS and disease progression

Objectives

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Results

Conclusion