Overexpression of Ras-GTPase-activating protein SH3 domain-binding protein 1 correlates with poor prognosis in gastric cancer patients
Overexpression of Ras-GTPase-activating protein SH3 domain-binding protein 1 correlates with poor prognosis in gastric cancer patients
复制标题
Ras-GTPase 激活蛋白 SH3 结构域结合蛋白 1 的过度表达与胃癌患者的不良预后相关。
DOI：
10.1111/his.12695
复制
发表时间：
2015-11-01
期刊：
影响因子：
6.4
通讯作者：
Gu, Jianxin
中科院分区：
文献类型：
--
作者：
Min, Lingqiang;Ruan, Yuanyuan;Gu, Jianxin
目的：Ras- gtpase激活蛋白SH3结构域结合蛋白1 （G3BP1）是Ras信号传导的下游效应蛋白，在几种人类恶性肿瘤中过表达。然而，其在胃癌中的作用尚不清楚。本研究旨在探讨G3BP1在胃癌中的预后意义。方法和结果采用实时聚合酶链反应和western blotting检测配对冷冻肿瘤标本中g3bp1 mRNA和蛋白水平。石蜡包埋肿瘤样本进行免疫组织化学。用胃癌细胞检测G3BP1的体外致瘤作用。我们发现胃癌组织中G3BP1蛋白的表达与相应的非恶性粘膜相比明显升高，而mRNA水平未见相应的变化。G3BP1染色与肿瘤大小、血管浸润、T分型、淋巴结转移、TNM分期、总生存率降低呈正相关。进一步分析发现G3BP1是不良预后的独立预后因素，将G3BP1与TNM分期相结合可以更好地预测患者预后。G3BP1还能促进胃癌细胞的增殖、迁移/侵袭以及细胞外信号相关激酶和AKT的激活。结论sour数据表明G3BP1是一个与胃癌进展相关的新的独立预后因子。
AimsRas-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a downstream effector of Ras signalling, and is overexpressed in several types of human malignancy. However, its role in gastric cancer remains unclear. The aim of this study was to investigate the prognostic significance of G3BP1 in gastric cancer.Methods and resultsG3BP1 mRNA and protein levels in paired frozen tumour samples were detected by real-time polymerase chain reaction and western blotting, respectively. Paraffin-embedded tumour samples were used for immunohistochemistry. Gastric cancer cells were used to detect the tumorigenic role of G3BP1 invitro. We found that G3BP1 protein expression was markedly increased in gastric cancer tissues as compared with corresponding non-malignant mucosa, whereas corresponding changes in mRNA levels were not observed. G3BP1 staining was positively correlated with tumour size, vascular invasion, T classification, lymph node metastasis, TNM stage, and reduced overall survival. Further analysis identified G3BP1 as an independent prognostic factor for poor prognosis, and combining G3BP1 with TNM stage generated a better predictive model for patient outcomes. G3BP1 also promoted proliferation, migration/invasion and extracellular signal-related kinase and AKT activation in gastric cancer cells.ConclusionsOur data define G3BP1 as a novel independent prognostic factor that is correlated with gastric cancer progression.