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Yes相关蛋白在结直肠癌中的临床及预后意义

Clinical and prognostic significance of Yes-associated protein in colorectal cancer.

作者信息

Wang Yan, Xie Chengyao, Li Qingchang, Xu Ke, Wang Enhua

机构信息

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, North 2nd Road 92, Heping Ward, Shenyang, Liaoning Province, People's Republic of China.

出版信息

Tumour Biol. 2013 Aug;34(4):2169-74. doi: 10.1007/s13277-013-0751-x. Epub 2013 Apr 5.

Abstract

The Hippo signaling pathway is a critical regulator of organ size control during development, and its deregulation is associated with cancers. Acting downstream of this pathway, Yes-associated protein (YAP) was implicated in tumorigenesis. The present study aimed to explore the expression patterns and clinical significance of YAP in human colorectal cancer (CRC). In addition, we investigated the relationship between YAP expression and Wnt/β-catenin pathway activation in CRC. A total of 139 cases of CRC tissues were investigated by immunohistochemistry for the expression of YAP, cyclin D1, and β-catenin. The association between YAP expression and clinicopathologic features was analyzed. Our results showed that YAP was overexpressed in 52.5 % (73/139) cases of CRC and predominantly presented in the nucleus. There was an excellent correlation between YAP expression and pTNM stage (p = 0.0024). YAP expression in CRC was significantly correlated with nodal status (p = 0.0034), tumor status (p = 0.0382), and cyclin D1 overexpression (p < 0.0001). Importantly, YAP expression was associated with short overall survival (p < 0.001). Furthermore, patients with YAP-positive and nuclear β-catenin-positive profiles had worse overall survival. Univariate and multivariate analyses revealed that YAP expression was an independent prognostic indicator of CRC (p = 0.0207). Our results indicated that YAP overexpression contributed to the tumorigenesis and played a pivotal role in the progression in CRC, and the interaction of YAP and Wnt/β-catenin pathways needs further exploration.

摘要

Hippo信号通路是发育过程中器官大小控制的关键调节因子,其失调与癌症相关。Yes相关蛋白(YAP)作为该通路的下游因子,与肿瘤发生有关。本研究旨在探讨YAP在人类结直肠癌(CRC)中的表达模式及临床意义。此外,我们还研究了CRC中YAP表达与Wnt/β-连环蛋白通路激活之间的关系。通过免疫组织化学法对139例CRC组织进行检测,分析YAP、细胞周期蛋白D1和β-连环蛋白的表达情况,并分析YAP表达与临床病理特征之间的关联。结果显示,52.5%(73/139)的CRC病例中YAP呈过表达,且主要定位于细胞核。YAP表达与pTNM分期显著相关(p = 0.0024)。CRC中YAP表达与淋巴结状态(p = 0.0034)、肿瘤状态(p = 0.0382)及细胞周期蛋白D1过表达显著相关(p < 0.0001)。重要的是,YAP表达与总生存期短相关(p < 0.001)。此外,YAP阳性且细胞核β-连环蛋白阳性的患者总生存期更差。单因素和多因素分析显示,YAP表达是CRC的独立预后指标(p = 0.0207)。我们的结果表明,YAP过表达促进了CRC的肿瘤发生并在其进展中起关键作用,YAP与Wnt/β-连环蛋白通路之间的相互作用有待进一步探索。

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