Yes相关蛋白1在卵巢浆液性囊腺癌中的表达及其临床意义
Expression of Yes-associated protein 1 and its clinical significance in ovarian serous cystadenocarcinoma.
作者信息
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
机构信息
Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
出版信息
Oncol Rep. 2017 May;37(5):2620-2632. doi: 10.3892/or.2017.5517. Epub 2017 Mar 21.
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.
Yes相关蛋白1(YAP1)是Hippo信号通路中的关键转录调节因子,在包括卵巢癌在内的多种恶性肿瘤的发生和发展中起关键作用。在此,我们使用TCGA数据库,调查了YAP1在大量卵巢浆液性囊腺癌(OSC,上皮性卵巢肿瘤最常见的形式)患者中的表达及其临床意义。令人惊讶的是,在TCGA数据库中,OSC中YAP1的跨癌mRNA表达和改变高于其他类型的癌症。与正常卵巢样本相比,OSC中YAP1 mRNA表达显著更高,且在III期和IV期高于I期和II期。主要定位于细胞核的YAP1蛋白水平在IV期也高于I、II和III期。然而,无活性且定位于细胞质的pYAP1蛋白水平在各期之间无显著差异。pYAP/YAP比值在低比值时活性较高,在III期低于I期和II期。YAP高表达和pYAP低表达与OSC患者的不良预后显著相关。与分化型、免疫反应型和间充质型亚型相比,YAP1的mRNA和蛋白表达在增殖型亚型中显著增加。根据生物信息学分析,YAP1与细胞周期相关性最高。根据基因集富集分析,高YAP1组中TGF-β信号和WNT信号显著增加。综上所述,我们的结果表明,不仅YAP1高表达,而且其亚细胞分布可能与OSC患者的总体生存不良有关。