作者
L Zhang,Y C Wang,Xiaoying Xie,J Chen,Dongling Gao,Zheng-gang Ren
摘要
Objective: To investigate the association between expression of phosphoglycerate kinase 1 (PGK1) in liver cancer tissue and prognosis, as well as its influence on metastasis and invasion of hepatocellular carcinoma (HCC) cells. Methods: Overexpression and downregulated expression of PGK1 in HCC cells were mediated by lentivirus to establish hepatoma cell lines with different expression levels of PGK1. The Transwell chamber invasion assay, wound healing assay, and colony-forming assay were used to investigate the influence of PGK1 on metastasis, invasion, and proliferation of HCC cells. Immunohistochemistry was used to measure the expression of PGK1 in liver cancer tissue samples from 116 patients with hepatocellular carcinoma who underwent radical surgery, and the Kaplan-Meier method and the log-rank test were used to determine the association between PGK1 expression and prognosis of patients with liver cancer. Results: HCCLM3 and MHCC97H HCC cells with high metastatic potential had significantly higher expression of PGK1 than Hep3B and Huh7 HCC cells with low metastatic potential. Downregulation of PGK1 expression significantly inhibited the migration (31.2% ± 2.4% vs 12.0% ± 1.3%, t = 21.57, P < 0.01), invasion (58 ± 11 vs 21 ± 8, t = 4.687, P < 0.05), and colony-forming ability (168.6 ± 15.1 vs 118.4 ± 8.1, t = 6.650, P < 0.05) of MHCC97H cells, while overexpression of PGK1 enhanced the migration (62.8% ± 4.4% vs 83.6% ± 6.1%, t = 20.56, P < 0.01), invasion (80 ± 12 vs 121 ± 15, t = 4.603, P < 0.05), and colony-forming ability (52.3 ± 8.6 vs 84.7 ± 9.0, t = 27.18, P < 0.01) of Hep3B cells. The high PGK1 expression group had significantly shorter median disease-free survival time and mean survival time than the low PGK1 expression group (22.00 ± 8.51 vs not reached, P < 0.05; 46.00 ± 16.87 vs not reached, P < 0.01). Conclusions: PGK1 is involved in the regulation of metastasis and invasion of HCC cells and can promote the migration and invasion of HCC cells. Therefore, PGK1 may be an important predictor of prognosis and postoperative recurrence in patients with liver cancer.目的: 探讨磷酸甘油酸激酶(PGK)1在肝癌患者组织中的表达水平与其预后的关系及其对肝癌细胞侵袭、转移能力的影响。 方法: 通过慢病毒载体介导PGK1在肝癌细胞中过表达,以及下调PGK1的表达,构建不同PGK1表达水平的肝癌细胞株。采用Transwell小室侵袭、划痕和克隆形成实验,检测PGK1对肝癌细胞侵袭、转移和增殖能力的影响。免疫组织化学染色法检测116例肝细胞肝癌根治性手术患者的肝癌组织中PGK1的表达水平,应用Kaplan-Meier法和Log-rank检验分析PGK1表达水平与肝癌患者术后预后的关系。PGK1蛋白表达差异比较采用t检验分析。 结果: PGK1在高转移潜能HCCLM3、MHCC97H肝癌细胞株中的表达水平显著高于低转移潜能的Hep3B、Huh7肝癌细胞。下调PGK1表达可明显抑制MHCC97H肝癌细胞的运动(31.2%±2.4%与12.0%±1.3%,t = 21.57,P < 0.01)、侵袭[(58±11)个与(21±8)个,t = 4.687,P < 0.05)]和克隆形成能力[(168.6±15.1)个与(118.4±8.1)个,t = 6.250,P < 0.05];而过表达PGK1后,肝癌细胞Hep3B的运动(62.8%±4.4%与83.6%±6.1%,t = 20.56,P < 0.01)、侵袭[(80±12)个与(121±15)个,t = 4.603,P < 0.05)]和克隆形成能力[(52.3±8.6)个与(84.7±9.0)个,t = 27.18,P < 0.01]增强。PGK1高表达组的肝癌患者术后中位无瘤生存期和平均生存时间显著短于低表达组[(22.00±8.51)个月与尚未达到,P < 0.05;(46.00±16.87)个月与尚未达到, P < 0.01]。 结论: PGK1参与调节肝癌细胞转移和侵袭等生物学行为,具有促进肝癌细胞运动、侵袭能力的作用。PGK1是肝癌患者术后预后和复发的重要预测指标。.