Zhang Sheng, Wei Qing, Yang Yongzhi, Qin Huanlong, Li Xinxiang, Cai Sanjun, Ma Yanlei
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
J Cancer. 2019 Jan 1;10(3):689-696. doi: 10.7150/jca.28333. eCollection 2019.
Yes-associated protein (YAP) is a downstream effecter of Hippo signaling pathway, and has been linked to the initiation and development of colorectal cancer (CRC). However, the clinical significance of YAP in CRC remains controversial. This study was designed to investigate the clinical significance of YAP in CRC. We selected 206 eligible patients diagnosed with CRC from 2003 to 2007. Tissue microarray (TMA) blocks were made from 206 formalin-fixed paraffin-embedded CRC tissues and 158 corresponding normal colonic tissues. Using the TMA blocks, we performed immunohistochemical staining of YAP and assessed its expression status in different subcellular locations. The patients were divided into four groups according to the expression status of YAP in the cytoplasm and nucleus. Statistical analysis was performed to explore the correlation between YAP expression and clinicopathological features and overall survival (OS) in CRC patients. Our results showed that both cytoplasmic YAP and nuclear YAP were overexpressed in CRC tissues compared to normal colonic tissues. Complete loss of YAP expression in CRC was significantly correlated with larger tumor size (p=0.023), proximal tumor location (p=0.038), higher tumor grade (p=0.022) and worse OS (p<0.001). Univariate and multivariate Cox regression analyses revealed that complete loss of YAP expression was an independent indicator of poor prognosis in CRC (p<0.001). Loss of YAP expression correlates with poor prognosis and may represent a subgroup with more aggressive biological features in CRC.
Yes相关蛋白（YAP）是Hippo信号通路的下游效应器，与结直肠癌（CRC）的发生和发展有关。然而，YAP在CRC中的临床意义仍存在争议。本研究旨在探讨YAP在CRC中的临床意义。我们选取了2003年至2007年间确诊为CRC的206例合格患者。从206例福尔马林固定石蜡包埋的CRC组织和158例相应的正常结肠组织制作组织微阵列（TMA）块。利用TMA块，我们对YAP进行了免疫组织化学染色，并评估了其在不同亚细胞位置的表达状态。根据YAP在细胞质和细胞核中的表达状态将患者分为四组。进行统计分析以探讨YAP表达与CRC患者临床病理特征及总生存期（OS）之间的相关性。我们的结果显示，与正常结肠组织相比，CRC组织中细胞质YAP和细胞核YAP均过度表达。CRC中YAP表达完全缺失与肿瘤较大（p = 0.023）、肿瘤近端位置（p = 0.038）、肿瘤分级较高（p = 0.022）及OS较差（p < 0.001）显著相关。单因素和多因素Cox回归分析显示，YAP表达完全缺失是CRC预后不良的独立指标（p < 0.001）。YAP表达缺失与预后不良相关，可能代表CRC中具有更具侵袭性生物学特征的一个亚组。
