Open AccessHigh A20 expression negatively impacts survival in patients with breast cancer
Author(s) -
Chung Sik Yoon,
Sung Gwe Ahn,
Soong June Bae,
Yun Chang Shin,
Chihwan Cha,
So Eun Park,
Ji Hyung Lee,
Akira Ooshima,
Hye Sun Lee,
Kyung Min Yang,
SeongJin Kim,
Seok Hee Park,
Jeong Eon Lee
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0221721
Subject(s) - breast cancer , immunohistochemistry , oncology , medicine , cancer , triple negative breast cancer , metastasis , survival analysis
Background A20 protein has ubiquitin-editing activities and acts as a key regulator of inflammation and immunity. Previously, our group showed that A20 promotes tumor metastasis through multi-monoubiquitylation of SNAIL1 in basal-like breast cancer. Here, we investigated survival outcomes in patients with breast cancer according to A20 expression. Patients and methods We retrospectively collected tumor samples from patients with breast cancer. Immunohistochemistry (IHC) with an A20-specific antibody was performed, and survival outcomes were analyzed. Results A20 expression was evaluated in 442 patients. High A20 expression was associated with advanced anatomical stage and young age. High A20 expression showed significantly inferior recurrence-free-survival and overall-survival ( P< 0.001 and P <0.001, respectively). Multivariate analysis showed that A20 was an independent prognostic marker for RFS (HRs: 2.324, 95% CIs: 1.446–3.736) and OS (HRs: 2.629, 95% CIs: 1.585–4.361). In human epidermal growth factor receptor 2 (HER2)-positive and triple negative breast cancer (TNBC) subtypes, high A20 levels were associated with poor OS. Conclusion We found that A20 expression is a poor prognostic marker in breast cancer. The prognostic impact of A20 was pronounced in aggressive tumors, such as HER2-positive and TNBC subtypes. Our findings suggested that A20 may be a valuable target in patients with aggressive breast cancer.