Increased expression of glycinamide ribonucleotide transformylase is associated with a poor prognosis in hepatocellular carcinoma, and it promotes liver cancer cell proliferation
Increased expression of glycinamide ribonucleotide transformylase is associated with a poor prognosis in hepatocellular carcinoma, and it promotes liver cancer cell proliferation
复制标题
甘氨酰胺核糖核苷酸转化酶表达增加与肝细胞癌预后不良相关，并促进肝癌细胞增殖
DOI：
10.1016/j.humpath.2013.11.021
复制
发表时间：
2014-07-01
期刊：
影响因子：
3.3
通讯作者：
Ni, Runzhou
中科院分区：
文献类型：
--
作者：
Cong, Xia;Lu, Cuihua;Ni, Runzhou
甘氨酸酰胺核糖核苷酸转化酶（GART）是一种叶酸依赖性酶，在新的嘌呤途径中，近20年来一直是抗肿瘤干预的目标。迄今为止，其在肝细胞癌（HCC）中的表达及功能意义尚不清楚。我们通过Western blotting证实，在HCC患者中，GART的表达明显上调。采用免疫组化染色法测定了96例HCC及癌旁非肿瘤组织中GART的表达。GART的表达增加与组织学分级（P = 0.001）、肿瘤大小（P = 0.043）、肿瘤淋巴结数（P = 0.020）和肝内转移（P = 0.031）呈正相关，提示GART在HCC的进展中起作用。高表达的患者总生存率明显低于低表达的患者（P = 0.002）。此外，多因素分析显示，GART表达是总生存的独立预测因子（风险比2.265；95%可信区间1.335-3.842;P = 0.002）。在HepG2和BEL-7404细胞中，用小干扰RNA消耗GART抑制细胞增殖，阻断s期和有丝分裂进入。Western blot分析显示，GART的消耗降低了增殖细胞核抗原的浓度。总的来说，我们的临床和体外数据表明，GART表达可能是HCC预后不良的原因之一。(C) 2014爱思唯尔公司版权所有。
Glycinamide ribonucleotide transformylase (GART) is a folate-dependent enzyme in the de novo purine pathway that has been the target of antineoplastic intervention for almost 2 decades. Until now, its expression and functional significance in hepatocellular carcinoma (HCC) have been unclear. We demonstrated by Western blotting that the expression of GART was markedly up-regulated in HCC patients. Immunohistochemistry staining was used to determine the expression of GART in HCC and adjacent nontumor tissues from 96 patients. Increased expression of GART correlated positively with the histologic grade (P = .001), tumor size (P = .043), number of tumorous nodes (P = .020), and intrahepatic metastases (P = .031), suggesting a role for GART in the progression of HCC. Patients with higher GART expression had a much worse overall survival rate than those with low expression (P = .002). Furthermore, multivariate analysis showed that GART expression was an independent predictor of overall survival (hazard ratio, 2.265; 95% confidence interval, 1.335-3.842; P = .002). Depletion of GART by small interfering RNA inhibited cell proliferation and blocked S-phase and mitotic entry in cultured HepG2 and BEL-7404 cells. Western blot analyses showed that GART depletion decreased the proliferating cell nuclear antigen concentration. Collectively, our clinical and in vitro data indicate that GART expression may be one of the causative factors for a poor prognosis in HCC. (C) 2014 Elsevier Inc. All rights reserved.