Hong Soon Auck, Son Myoung Won, Cho Junhun, Jang Si-Hyong, Lee Hyun Ju, Lee Ji-Hye, Cho Hyun Deuk, Oh Mee-Hye, Lee Moon Soo
Department of Pathology, Soonchunhyang University Cheonan Hospital, College of Medicine, Soonchunhyang University, Cheonan, Korea.
Department of General Surgery, Soonchunhyang University Cheonan Hospital, College of Medicine, Soonchunhyang University, Cheonan, Korea.
APMIS. 2017 Nov;125(11):996-1006. doi: 10.1111/apm.12750. Epub 2017 Sep 8.
Angiomotin (AMOT) promotes angiogenesis and plays a role in neovascularization during tumorigenesis. Recently, the AMOT isoform, AMOT-p130, was shown to exert a regulatory effect on Yes-associated protein 1 (YAP1), a major downstream effector of the Hippo pathway. The specific roles of AMOT-p130 and YAP1 in advanced gastric cancer (AGC) are yet to be established. In this study, a total of 166 patients with AGC were enrolled, and AMOT-p130 and YAP1 levels were analyzed by immunohistochemistry using tissue microarrays. Low AMOT-p130 together with high YAP1 expression (n = 30, 18.1%) was associated with high T stage (p = 0.042), high TNM stage (p = 0.025), and venous invasion (p = 0.048). A Kaplan-Meier survival analysis with log-rank test revealed a significant correlation with decreased AMOT-p130 coupled with high nuclear YAP1 expression with shorter overall survival (p = 0.0045) and disease-free survival (p = 0.0028). Furthermore, multivariate analyses showed that the low AMOT-p130/high YAP1 expression profile was an independent prognostic factor for disease-free survival (p = 0.008, HR = 1.874, CI, 1.177-2.986) and overall survival (p = 0.012, HR = 1.903, CI, 1.152-3.143). Our findings collectively demonstrate that low AMOT-p130 combined with high YAP1 expression is correlated with an unfavorable AGC prognosis.
血管动蛋白(AMOT)可促进血管生成,并在肿瘤发生过程中的新生血管形成中发挥作用。最近,AMOT异构体AMOT-p130被证明对Yes相关蛋白1(YAP1)具有调节作用,YAP1是Hippo通路的主要下游效应因子。AMOT-p130和YAP1在进展期胃癌(AGC)中的具体作用尚待确定。在本研究中,共纳入了166例AGC患者,并使用组织微阵列通过免疫组织化学分析了AMOT-p130和YAP1水平。低AMOT-p130与高YAP1表达(n = 30,18.1%)与高T分期(p = 0.042)、高TNM分期(p = 0.025)和静脉侵犯(p = 0.048)相关。采用对数秩检验的Kaplan-Meier生存分析显示,AMOT-p130降低与高核YAP1表达与总生存期缩短(p = 0.0045)和无病生存期缩短(p = 0.0028)显著相关。此外,多因素分析表明,低AMOT-p130/高YAP1表达谱是无病生存期(p = 0.008,HR = 1.874,CI,1.177 - 2.986)和总生存期(p = 0.012,HR = 1.903,CI,1.152 - 3.143)的独立预后因素。我们的研究结果共同表明,低AMOT-p130与高YAP1表达与AGC预后不良相关。