High A20 expression negatively impacts survival in patients with breast cancer.

• Main Authors: Chang Ik Yoon, Sung Gwe Ahn, Soong June Bae, Yun Jin Shin, Chihwan Cha, So Eun Park, Ji-Hyung Lee, Akira Ooshima, Hye Sun Lee, Kyung-Min Yang, Seong-Jin Kim, Seok Hee Park, Joon Jeong
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2019-01-01
• Series: PLoS ONE
• Online Access: https://doi.org/10.1371/journal.pone.0221721

<h4>Background</h4>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.<h4>Patients and methods</h4>We retrospectively collected tumor samples from patients with breast cancer. Immunohistochemistry (IHC) with an A20-specific antibody was performed, and survival outcomes were analyzed.<h4>Results</h4>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.<h4>Conclusion</h4>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.