Zhang L, Wang Y C, Xie X Y, Chen J, Gao D M, Ren Z G
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, China.
Zhonghua Gan Zang Bing Za Zhi. 2017 Jun 20;25(6):446-451. doi: 10.3760/cma.j.issn.1007-3418.2017.06.011.
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. 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. 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%, = 21.57, < 0.01), invasion (58 ± 11 vs 21 ± 8, = 4.687, < 0.05), and colony-forming ability (168.6 ± 15.1 vs 118.4 ± 8.1, = 6.650, < 0.05) of MHCC97H cells, while overexpression of PGK1 enhanced the migration (62.8% ± 4.4% vs 83.6% ± 6.1%, = 20.56, < 0.01), invasion (80 ± 12 vs 121 ± 15, = 4.603, < 0.05), and colony-forming ability (52.3 ± 8.6 vs 84.7 ± 9.0, = 27.18, < 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, < 0.05; 46.00 ± 16.87 vs not reached, < 0.01). 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.
探讨肝癌组织中磷酸甘油酸激酶1（PGK1）的表达与预后的关系，以及其对肝癌（HCC）细胞转移和侵袭的影响。通过慢病毒介导HCC细胞中PGK1的过表达和下调表达，建立具有不同PGK1表达水平的肝癌细胞系。采用Transwell小室侵袭试验、伤口愈合试验和集落形成试验，研究PGK1对HCC细胞转移、侵袭和增殖的影响。应用免疫组织化学法检测116例行根治性手术的肝细胞癌患者肝癌组织样本中PGK1的表达，采用Kaplan-Meier法和对数秩检验确定PGK1表达与肝癌患者预后的关系。具有高转移潜能的HCCLM3和MHCC97H HCC细胞中PGK1的表达明显高于具有低转移潜能的Hep3B和Huh7 HCC细胞。PGK1表达下调显著抑制了MHCC97H细胞的迁移（31.2%±2.4%对12.0%±1.3%，P = 21.57，P<0.01）、侵袭（58±11对21±8，P = 4.687，P<0.05）和集落形成能力（168.6±15.1对118.4±8.1，P = 6.650，P<0.05），而PGK1过表达增强了Hep3B细胞的迁移（62.8%±4.4%对83.6%±6.1%，P = 20.56，P<0.01）、侵袭（80±12对121±15，P = 4.603，P<0.05）和集落形成能力（52.3±8.6对84.7±9.0，P = 27.18，P<0.01）。PGK1高表达组的中位无病生存期和平均生存期明显短于PGK1低表达组（22.00±8.51对未达到，P<0.05；46.00±16.87对未达到，P<0.01）。PGK1参与HCC细胞转移和侵袭的调控，可促进HCC细胞的迁移和侵袭。因此，PGK1可能是肝癌患者预后和术后复发的重要预测指标。
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