Coexistence of YWHAZ amplification predicts better prognosis in muscle-invasive bladder cancer with CDKN2A or TP53 loss

Abstract

The amplification of YWHAZ was commonly seen in bladder cancer. We explore the biological significance of YWHAZ amplification on bladder cancer, and the correlation with important other molecular events. The Cancer Genome Atlas (TCGA) database was exploited to study the impact of YWHAZ amplification on either CDKN2A or TP53 mutations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was also exploited to clustering of enriched genes in the cBioPortal Enrichment tests. There were 127 cases with available mutation and CNV data in the corresponding TCGA bladder cancer dataset, 20% of them had YWHAZ alteration. Patients with both YWHAZ amplification and CDKN2A loss demonstrated significantly better overall survival (OS) compared with CDKN2A loss alone. Patients with both YWHAZ amplification and TP53 mutation demonstrated significantly better overall survival (OS) and disease-free survival (DFS) compared with TP53 mutation alone. The amplification of YWHAZ, along with alteration of CDKN2A or TP53, predict better survival in bladder cancers that only had CDKN2A or TP53 alteration. The protective role of YWHAZ in bladder cancer deserve insightful further studies.

Knockdown of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) enhances tumorigenesis both in vivo and in vitro in bladder cancer

“…To the best of our knowledge, scarce studies have focused on YWHAZ and its coding protein, 14-3-3ζ on bladder cancer. Thus, this study was an innovative attempt and these findings were also in accordance with the results of our previous study that YWHAZ amplification predicts better survival, under the background of some anti-oncogene loss such as TP53 and CDKN2A ( 10 ).…”

“…Since CDC25 have varieties of isoforms, the affinity of 14-3-3ζ to different CDC25 isoforms remains to be explored. Moreover, this could explain our findings in a previous study that YWHAZ amplification significantly benefited survival outcomes under the background of CDKN2A or TP53 loss, both critical factors in cell cycle regulation ( 10 ). The malfunction of CDKN2A or TP53 causes disruption of cell cycle control and enhancement of proliferation.…”

“…In our previous study, we revealed that the amplification of YWHAZ , along with TP53 or CDKN2A loss predicted better survival ( 10 ). This finding demonstrated that YWHAZ may play an antitumor effect in bladder cancer development.…”

YWHAZ amplification/overexpression defines aggressive bladder cancer and contributes to chemo‐/radio‐resistance by suppressing caspase‐mediated apoptosis

“…YWHAZ amplification is also reported to be clinically significant in other cancer types, including breast , prostate , lung , and oral cancers. Although YWHAZ has also been reported to act as a tumor suppressor during bladder cancer development , our results consistently show that YWHAZ overexpression negatively regulates apoptosis, enabling cellular adaptation to the presence of chemotherapeutic drugs. In contrast to anti‐apoptotic effects, other proteins participating in diverse functions/pathways within cells were found to be upregulated along with YWHAZ overexpression (see supplementary material, Tables S3 and S4).…”

Inhibition of Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Zeta (YWHAZ) Overcomes Drug Resistance and Tumorigenicity in Ovarian Cancer

“…YWHAZ is involved in several cellular processes such as cell growth, differentiation, mitosis, and oncogenic transformation [17][18][19]. YWHAZ could serve as a promising prognostic biomarker in localized PCa to predict poor prognosis and to identify a subgroup of tumors [20].…”