High Nuclear Expression of Yes-Associated Protein 1 (YAP1) Correlates with Metastasis in Patients with Breast Cancer

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 is controversial. Here, we investigated the impact of different levels of nuclear YAP1 expression on the clinical characteristics and survival outcome of patients with breast cancer.Patients and Methods: Retrospectively obtained 469 breast tumor samples at the 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 489 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), and also confirmed 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 1.947, 95% CIs 1.003-3.779, P=0.049).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.