AUTHOR=Cha Yoon Jin , Bae Soong June , Kim Dooreh , Ahn Sung Gwe , Jeong Joon , Koo Ja Seung , Yoo Tae-Kyung , Park Woo-Chan , Lee Ahwon , Yoon Chang Ik TITLE=High Nuclear Expression of Yes-Associated Protein 1 Correlates With Metastasis in Patients With Breast Cancer JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.609743 DOI=10.3389/fonc.2021.609743 ISSN=2234-943X ABSTRACT=Background

Yes-associated protein 1 (YAP1) is a transcription factor regulated by the Hippo pathway and functions as an oncogene in various solid tumors under dysregulated Hippo pathway. However, the role of YAP1 in breast cancer remains controversial. Here, we investigated the impact of different levels of nuclear YAP1 expression on the clinical characteristics and survival outcome in patients with breast cancer.

Patients and Methods

Retrospectively obtained 455 breast tumor samples at Gangnam Severance Hospital were examined for YAP1 expression by immunohistochemistry, and the clinical data were analyzed. External validation was performed using a retrospective cohort and tissues in 482 patients from Severance Hospital.

Results

High nuclear YAP1 expression was associated with hormone receptor negativity and aggressive tumor behavior, including lymph node metastasis, high Ki67 labeling index and inferior distant metastasis-free survival (DMFS, hazard ratio [HR] 2.271, 95% confidence intervals [CIs] 1.109–4.650, P = 0.0249), and also confirmed inferior disease free survival (HR 3.208, 95% CIs 1.313–7.833, P = 0.0105) in external validation cohort. In patients with triple-negative breast cancer (TNBC), high nuclear YAP1 expression was an independent significant determinant of poor DMFS (HR 2.384, 95% CIs 1.055–5.386, P = 0.0367).

Conclusion

Our findings suggest that nuclear YAP1 expression is a biomarker of adverse prognosis and a potential therapeutic target in patients with breast cancer, especially in TNBC.