Research Paper Volume 12, Issue 19 pp 19597—19617
Characterization of the expression and prognostic value of 14-3-3 isoforms in breast cancer
- 1 Department of Oncology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu, P.R. China
- 2 Department of Physiology, Nanjing Medical University, Nanjing 211166, Jiangsu, P.R. China
- 3 Department of General Surgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu, P.R. China
- 4 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, Jiangsu, P.R. China
Received: January 12, 2020 Accepted: July 25, 2020 Published: October 14, 2020
https://doi.org/10.18632/aging.103919How to Cite
Copyright: © 2020 Mei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation proteins (14-3-3) participate in the tumorigenesis and progression of numerous malignances, but their precise prognostic values in breast cancer (BrCa) remain unknown. Here, we investigated the expression profiles and prognostic roles of 14-3-3 isoforms by employing multiple online databases. The transcriptional levels of most 14-3-3 isoforms in BrCa tissues were significantly higher than those in normal tissues. High mRNA expression of 14-3-3 beta/sigma/theta/zeta was significantly associated with poor overall survival (OS) in BrCa patients, while high mRNA expression of 14-3-3 epsilon was notably related to favorable OS. High mRNA expression of 14-3-3 beta/gamma/sigma/theta/zeta was significantly associated with poor relapse-free survival (RFS) in BrCa patients. A high mutation rate of 14-3-3 was determined to be associated with poor clinical outcomes. In addition, 14-3-3 expression was correlated with the infiltration of specific immune cells types. Analysis of the breast-specific protein-protein interaction (PPI) network suggested that 14-3-3 proteins were involved in several potential oncogenic mechanisms in BrCa. Finally, we performed experimentally validated their oncogenic roles in BrCa. Overall, our findings systematically elucidate the expression and distinct prognostic value of 14-3-3 isoforms in BrCa, which may provide potential therapeutic targets and prognostic biomarkers for BrCa.
Abbreviations
BrCa: breast cancer; 14-3-3: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation proteins; MAPK: mitogen activated protein kinase; DAAM1: dishevelled associated activator of morphogenesis 1; PPI: protein-protein interaction; OS: overall survival; RFS: relapse-free survival; DFS: disease-free survival; CNAs: copy number alterations; TIICs: tumor-infiltrating immune cells; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; IHC: immunohistochemistry; EMT: epithelial-mesenchymal transition; HR: hazard ratio; 95%CI: 95% confidence interval; FDR: false discovery rate; TMA: tumor tissue microarray; IRS: immunoreactivity score; FBS: fetal bovine serum.