Cargando…

High Nuclear Expression of Yes-Associated Protein 1 Correlates With Metastasis in Patients With Breast Cancer

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947190/
https://www.ncbi.nlm.nih.gov/pubmed/33718163
http://dx.doi.org/10.3389/fonc.2021.609743
_version_ 1783663169739161600
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
author_facet 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
author_sort Cha, Yoon Jin
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7947190
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-79471902021-03-12 High Nuclear Expression of Yes-Associated Protein 1 Correlates With Metastasis in Patients With Breast Cancer 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 Front Oncol Oncology 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. Frontiers Media S.A. 2021-02-25 /pmc/articles/PMC7947190/ /pubmed/33718163 http://dx.doi.org/10.3389/fonc.2021.609743 Text en Copyright © 2021 Cha, Bae, Kim, Ahn, Jeong, Koo, Yoo, Park, Lee and Yoon http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
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
High Nuclear Expression of Yes-Associated Protein 1 Correlates With Metastasis in Patients With Breast Cancer
title High Nuclear Expression of Yes-Associated Protein 1 Correlates With Metastasis in Patients With Breast Cancer
title_full High Nuclear Expression of Yes-Associated Protein 1 Correlates With Metastasis in Patients With Breast Cancer
title_fullStr High Nuclear Expression of Yes-Associated Protein 1 Correlates With Metastasis in Patients With Breast Cancer
title_full_unstemmed High Nuclear Expression of Yes-Associated Protein 1 Correlates With Metastasis in Patients With Breast Cancer
title_short High Nuclear Expression of Yes-Associated Protein 1 Correlates With Metastasis in Patients With Breast Cancer
title_sort high nuclear expression of yes-associated protein 1 correlates with metastasis in patients with breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947190/
https://www.ncbi.nlm.nih.gov/pubmed/33718163
http://dx.doi.org/10.3389/fonc.2021.609743
work_keys_str_mv AT chayoonjin highnuclearexpressionofyesassociatedprotein1correlateswithmetastasisinpatientswithbreastcancer
AT baesoongjune highnuclearexpressionofyesassociatedprotein1correlateswithmetastasisinpatientswithbreastcancer
AT kimdooreh highnuclearexpressionofyesassociatedprotein1correlateswithmetastasisinpatientswithbreastcancer
AT ahnsunggwe highnuclearexpressionofyesassociatedprotein1correlateswithmetastasisinpatientswithbreastcancer
AT jeongjoon highnuclearexpressionofyesassociatedprotein1correlateswithmetastasisinpatientswithbreastcancer
AT koojaseung highnuclearexpressionofyesassociatedprotein1correlateswithmetastasisinpatientswithbreastcancer
AT yootaekyung highnuclearexpressionofyesassociatedprotein1correlateswithmetastasisinpatientswithbreastcancer
AT parkwoochan highnuclearexpressionofyesassociatedprotein1correlateswithmetastasisinpatientswithbreastcancer
AT leeahwon highnuclearexpressionofyesassociatedprotein1correlateswithmetastasisinpatientswithbreastcancer
AT yoonchangik highnuclearexpressionofyesassociatedprotein1correlateswithmetastasisinpatientswithbreastcancer