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高表达的 A20 对乳腺癌患者的生存产生负面影响。

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

机构信息

Department of Surgery, St Mary's Hospital, Catholic University College of Medicine, Seoul, Korea.

Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

出版信息

PLoS One. 2019 Aug 26;14(8):e0221721. doi: 10.1371/journal.pone.0221721. eCollection 2019.

DOI:10.1371/journal.pone.0221721
PMID:31449546
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6709902/
Abstract

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.

摘要

背景

A20 蛋白具有泛素化修饰活性，是炎症和免疫的关键调节因子。我们之前的研究表明，A20 通过多泛素化基底样乳腺癌中的 SNAIL1 促进肿瘤转移。在此，我们根据 A20 表达情况分析了乳腺癌患者的生存结局。

患者和方法

我们回顾性收集了乳腺癌患者的肿瘤样本。采用 A20 特异性抗体进行免疫组织化学（IHC）检测，并分析生存结局。

结果

对 442 例患者进行了 A20 表达评估。A20 高表达与解剖学晚期和年轻有关。A20 高表达的患者无复发生存率和总生存率显著降低（P<0.001 和 P<0.001）。多因素分析表明，A20 是 RFS（HR：2.324，95%CI：1.446-3.736）和 OS（HR：2.629，95%CI：1.585-4.361）的独立预后标志物。在人表皮生长因子受体 2（HER2）阳性和三阴性乳腺癌（TNBC）亚型中，A20 水平高与 OS 不良相关。

结论

我们发现 A20 表达是乳腺癌的不良预后标志物。A20 在 HER2 阳性和 TNBC 等侵袭性肿瘤中的预后影响更为显著。我们的研究结果表明，A20 可能是侵袭性乳腺癌患者的一个有价值的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8061/6709902/04ee8d91054d/pone.0221721.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8061/6709902/3d998108395e/pone.0221721.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8061/6709902/04ee8d91054d/pone.0221721.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8061/6709902/3d998108395e/pone.0221721.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8061/6709902/04ee8d91054d/pone.0221721.g002.jpg

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