Huang Xiaodong, Cong Xia, Yang Dunpeng, Ji Lili, Liu Yanhua, Cui Xiaopeng, Cai Jing, He Song, Zhu Changyun, Ni Runzhou, Zhang Yixin
Department of Pathology, Nantong University Cancer Hospital, Nantong, Jiangsu 226001, PR China; Department of Digestion, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China.
Department of Digestion, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China.
Pathol Res Pract. 2014 Nov;210(11):719-25. doi: 10.1016/j.prp.2014.07.001. Epub 2014 Jul 17.
GTP binding protein overexpressed in skeletal muscle (Gem) is a Ras-related protein whose expression is induced in several cell types upon activation by extracellular stimuli. To investigate the potential roles of Gem in hepatocellular carcinoma (HCC), expression of Gem was examined in human HCC samples. Western blot analysis showed that compared with primary human hepatocytes and adjacent noncancerous tissue, significant down-regulation of Gem was found in HCC cells and tumor tissues. In addition, immunohistochemical analysis of Gem expression was investigated in 108 specimens of HCC tissues. Clinicopathological data were collected to analyze the association with Gem expression. Expression of Gem was significantly negatively correlated with histological grade (P=0.001), tumor size (P=0.020), and vascular invasion (P=0.005), and Gem was also negatively correlated with proliferation marker Ki-67 (P<0.01). More importantly, the Kaplan-Meier survival curves analysis revealed that low expression of Gem was associated with poor prognosis in HCC patients. Univariate analysis showed that Gem expression was associated with poor prognosis (P=0.006). Multivariate analysis indicated that Gem expression was an independent prognostic marker for HCC (P=0.007). Finally, serum starvation and release experiments showed that Gem expression was negatively related with cell proliferation. In the conclusion, our results suggested that down regulation of Gem expression was involved in the pathogenesis of hepatocellular carcinoma, and it might be a favorable independent prognostic parameter for HCC.
在骨骼肌中过表达的GTP结合蛋白（Gem）是一种与Ras相关的蛋白，其表达在几种细胞类型中被细胞外刺激激活后被诱导。为了研究Gem在肝细胞癌（HCC）中的潜在作用，检测了Gem在人HCC样本中的表达。蛋白质印迹分析表明，与原代人肝细胞和相邻的非癌组织相比，在HCC细胞和肿瘤组织中发现Gem显著下调。此外，对108例HCC组织标本进行了Gem表达的免疫组织化学分析。收集临床病理数据以分析与Gem表达的相关性。Gem的表达与组织学分级（P = 0.001）、肿瘤大小（P = 0.020）和血管侵犯（P = 0.005）显著负相关，Gem也与增殖标志物Ki-67负相关（P < 0.01）。更重要的是，Kaplan-Meier生存曲线分析显示，Gem低表达与HCC患者的预后不良相关。单因素分析表明，Gem表达与预后不良相关（P = 0.006）。多因素分析表明，Gem表达是HCC的独立预后标志物（P = 0.007）。最后，血清饥饿和释放实验表明，Gem表达与细胞增殖呈负相关。总之，我们的结果表明，Gem表达下调参与了肝细胞癌的发病机制，并且它可能是HCC一个良好的独立预后参数。
