Expression of Yes-associated protein 1 and its clinical significance in ovarian serous cystadenocarcinoma

Cho,Sang  Yeon; Kim,Kwanghun; Park,Min  Soo; Jang,Mi  Young; Choi,Young  Hwan; Han,Suyeon; Shin,Hyun  Mo; Chung,Chaeuk; Han,Hye  Young; Yang,Jung  Bo; Ko,Young  Bok; Yoo,Heon  Jong

doi:10.3892/or.2017.5517

Expression of Yes-associated protein 1 and its clinical significance in ovarian serous cystadenocarcinoma

Authors:
- Sang Yeon Cho
- Kwanghun Kim
- Min Soo Park
- Mi Young Jang
- Young Hwan Choi
- Suyeon Han
- Hyun Mo Shin
- Chaeuk Chung
- Hye Young Han
- Jung Bo Yang
- Young Bok Ko
- Heon Jong Yoo
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Affiliations: Chungnam National University School of Medicine, Daejeon, Republic of Korea, Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea, Department of Pulmonary and Critical Care Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea, Department of Pediatrics, Chungnam National University, Daejeon, Republic of Korea, Department of Obstetrics and Gynecology, Chungnam National University College of Medicine, Daejeon, Republic of Korea
Published online on: March 21, 2017 https://doi.org/10.3892/or.2017.5517
Pages: 2620-2632
Copyright: © Cho et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Yes-associated protein 1 (YAP1) is a key transcriptional regulator in the Hippo signaling pathway that plays a critical role in the development and progression of several types of malignancies, including ovarian cancer. Herein, we investigated the expression of YAP1 and its clinical significance in a large population of patients with ovarian serous cystadenocarcinoma (OSC), which is the most common form of epithelial ovarian neoplasm, using the TCGA database. Surprisingly, cross-cancer mRNA expression and alterations in YAP1 were higher in OSC than in those of other types of cancers in the TCGA database. YAP1 mRNA expression was significantly higher in OSC compared with normal ovarian samples, and was higher in stages III and IV, than stages I and II. The level of YAP1 protein, which is mainly localized to the nucleus, was also higher in stage IV as compared with stages I, II and III. However, the protein level of pYAP1, which is inactive and is localized to the cytoplasm, was not significantly different between stages. The ratio of pYAP/YAP, which shows higher activity at a low ratio, was lower in stage III than in stages I and II. High YAP and low pYAP levels were significantly correlated with a poor prognosis in patients with OSC. The mRNA and protein expression of YAP1 were significantly increased in the proliferative subtype as compared to the differentiated, immunoreactive and mesenchymal subtypes. According to bioinformatics analysis, YAP1 is most highly correlated with the cell cycle. TGF-β signaling and WNT signaling were significantly increased in the high YAP1 group according to gene set enrichment analysis. Taken together, our results suggest that not only high YAP1 expression but also its subcellular distribution may be associated with poor overall survival in patients with OSC.

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