The Hippo signaling effector WWTR1 is a metastatic biomarker of gastric cardia adenocarcinoma
The Hippo signaling effector WWTR1 is a metastatic biomarker of gastric cardia adenocarcinoma
复制标题
Hippo信号效应子WWTR1是胃贲门腺癌的转移生物标志物
DOI：
10.1186/s12935-019-0796-z
复制
发表时间：
2019-03-29
影响因子：
5.8
通讯作者：
Lin, Qiong
中科院分区：
文献类型：
--
作者：
Wei, Jing;Wang, Lincui;Lin, Qiong
研究背景贲门腺癌(Gca)是胃癌的一种侵袭性亚型，转移率高。方法应用组织芯片技术(TMA)检测214例GCA患者肿瘤组织中Hppo信号效应因子WWTR1(WW域含转录调节因子1，通常被称为TAZ)的表达，统计分析WWTR1的表达与GCA患者转移相关的病理结果和累积生存期的关系。结果：在66.4%的GCA肿瘤组织中，WWTR1过表达。WWTR1的表达与GCA患者的累积生存期呈显著负相关(p <； 0.01)。WWTR1阳性患者的平均生存期为56.9 ± 4.4月，而阴性患者的平均生存期为77.3 ± 5.9月。更重要的是，WWTR1的表达与肿瘤的侵袭和转移密切相关(T分期，p = 0.031；N分期，p 和lt； ；0.001；TNM分期，p 和lt； 0.001)。结论WWTR1是GCA预后不良的转移标志物，明确了WWTR1在胃癌转移中的作用，提示WWTR1可作为GCA抗转移治疗的潜在靶点。
BackgroundGastric cardia adenocarcinoma (GCA) is an aggressive subtype of gastric cancer with a high metastatic rate. However, the metastatic biomarker of GCA has not been established.MethodsTo search for the biomarker for GCA metastasis, we here examined expression of the Hippo signaling effector WWTR1 (WW domain containing transcription regulator 1, commonly listed as TAZ) in tumor tissue samples from 214 GCA cases using the tissue microarray assay (TMA), and statistically analyzed association of the WWTR1 expression with metastasis-related pathological outcomes and cumulative survival of the GCA patients. Furthermore, shRNA knockdown was used to determine the role of WWTR1 in promoting cell migration in gastric cancer cells.ResultsThe results have shown that WWTR1 is overexpressed in 66.4% of the GCA tumor samples. Expression of WWTR1 has a significant inverse correlation with cumulative survival of GCA patients (p < 0.01). WWTR1 positive patients had a mean survival of 56.9 ± 4.4 months, comparing to WWTR1 negative mean survival of 77.3 ± 5.9 months. More importantly, expression of WWTR1 significantly associated with tumor invasion and metastasis (in T stage, p = 0.031; N stage, p < 0.01; and TNM stage, p < 0.001). Furthermore, knockdown of WWTR1 impaired migration of gastric cancer AGS cells.ConclusionsOur studies have identified WWTR1 as a metastatic biomarker of GCA for poor prognosis, defined a role of WWTR1 in driving metastasis of gastric cancer, and suggested WWTR1 as a potential target for anti-metastatic therapy of GCA.