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

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.

Exploiting Interdata Relationships in Prostate Cancer Proteomes: Clinical Significance of HO-1 Interactors

“…Considering that: (1) YWHAZ has been reported to be an independent and strong predictor of aggressiveness in PCa [ 38 ]; (2) its expression showed a significant negative correlation with HMOX1 expression; (3) PCa patients with high YWHAZ/HMOX1 showed the highest HR; and (4) high YWHAZ was the only factor significantly associated with a higher risk of relapse; we validated the interaction between HO-1 and 14-3-3ζ/δ. PC3 cells were treated with H 2 O 2 or vehicle, and protein eluates were subjected to co-immunoprecipitation.…”

“…Members of the 14-3-3 protein family are involved in the regulation of a wide spectrum of signaling pathways by binding to various proteins [ 45 ] and contributing to the regulation of crucial cellular processes such as protein trafficking, malignant transformation, and differentiation [ 46 , 47 ]. Particularly, the ζ/δ isoform constitutes a potential prognostic and therapeutic target since its high expression correlates with the progression of different cancers [ 38 , 48 , 49 ]. Previous studies from our group demonstrated YWHAZ relevance as a prognostic factor independent from the clinic-pathological parameters associated with the disease, such as age, GS, and TMPRSS2-ERG fusion [ 38 ].…”

“…Particularly, the ζ/δ isoform constitutes a potential prognostic and therapeutic target since its high expression correlates with the progression of different cancers [ 38 , 48 , 49 ]. Previous studies from our group demonstrated YWHAZ relevance as a prognostic factor independent from the clinic-pathological parameters associated with the disease, such as age, GS, and TMPRSS2-ERG fusion [ 38 ]. Moreover, we observed that PCa patients with amplification, or increased mRNA or protein levels for YWHAZ , have significant alterations in key DNA repair genes [ 38 ].…”

“…Previous studies from our group demonstrated YWHAZ relevance as a prognostic factor independent from the clinic-pathological parameters associated with the disease, such as age, GS, and TMPRSS2-ERG fusion [ 38 ]. Moreover, we observed that PCa patients with amplification, or increased mRNA or protein levels for YWHAZ , have significant alterations in key DNA repair genes [ 38 ].…”

Claudin‐2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription

“… 35 Furthermore, NDRG1 overexpression inhibited glioblastoma cell growth by decreasing expression of cyclin D1/E and CDK 2/4 in a cell‐cycle signalling pathway. 36 Thus, some reports suggested NDRG1 as a poor prognostic predictor in prostate cancer 37 and inflammatory breast cancer. 38 However, other studies implied that NDRG1 may functions in tumour microenvironment remodelling.…”