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.