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

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-? 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.

SUBMITTER: Cho SY

PROVIDER: S-EPMC5428545 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Cho Sang Yeon SY Kim Kwanghun K Park Min Soo MS Jang Mi Young MY Choi Young Hwan YH Han Suyeon S Shin Hyun Mo HM Chung Chaeuk C Han Hye Young HY Yang Jung Bo JB Ko Young Bok YB Yoo Heon Jong HJ

Oncology reports 20170321 5

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 expr ...[more]

PMID: 28339095

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Project description:BackgroundOvarian serous cystadenocarcinoma (OSC) is the most common and lethal gynecological cancer in women worldwide; however, biomarkers to diagnose and predict prognosis of OSC remain limited. Therefore, the present study aimed to investigate whether sodium/potassium adenosine triphosphate (Na+/K+-ATP)ase α-subunits (ATP1As) are helpful diagnostic and prognostic markers of OSC.MethodsGene expression data (RNA-Seq) of 376 patients with OSC were downloaded from The Cancer Genome Atlas (TCGA) program database. Additional databases used in our analysis included the Gene Expression Omnibus, International Cancer Genome Consortium, Genotype-Tissue Expression, the Human Protein Atlas, cBioPortal for Cancer Genomics, and Cancer Cell Line Encyclopedia.ResultsThe expression levels of ATP1A1 and ATP1A3 were higher in OSC tissues than in normal ovarian tissues, whereas the expression levels of ATP1A2 and ATP1A4 were lower in OSC tissues than in normal ovarian tissues. Overexpression of ATP1A2 was significantly associated with a higher Federation of Gynecology and Obstetrics (FIGO) stage and histological grade. Increased mRNA expression of ATP1A3 was significantly associated with shorter overall survival (OS) and disease-specific survival (DSS) in patients with OSC, whereas higher expression of ATP1A4 was associated with favorable OS and DSS. Multivariate analysis showed that primary therapy outcome, residual tumor, and mRNA expressions of ATP1A3 and ATP1A4 were independent prognostic factors for both OS and DSS in patients with OSC. Moreover, ATP1A1 staining was abundant in tumor tissues. A high expression of ATP1A3 was significantly correlated with poor OS and DSS in the subgroup of patients aged ≥ 60 years and with FIGO stage III, histological grade G3, and TP53 mutation. Mutation frequencies of the ATP1As were 3-5%.ConclusionsThese results indicate that the ATP1A gene family could be potential diagnostic or prognostic markers of OSC. In addition, ATP1As may be effective therapeutic targets in the treatment of OSC.

Dataset Information

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

Publications

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

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