Expression of Yes-associated protein 1 and its clinical significance in ovarian serous cystadenocarcinoma.
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.
Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Sang Yeon
SY
Cho
Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kwanghun
K
Kim
Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Min Soo
MS
Park
Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Mi Young
MY
Jang
Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Young Hwan
YH
Choi
Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Suyeon
S
Han
Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
Hyun Mo
HM
Shin
Department of Pulmonary and Critical Care Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
Chaeuk
C
Chung
Department of Pediatrics, Chungnam National University, Daejeon, Republic of Korea.
Hye Young
HY
Han
Department of Obstetrics and Gynecology, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
Jung Bo
JB
Yang
Department of Obstetrics and Gynecology, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
Young Bok
YB
Ko
Department of Obstetrics and Gynecology, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
Heon Jong
HJ
Yoo
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human