Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Int J Cancer. 2012 Jan 15;130(2):319-27. doi: 10.1002/ijc.25994. Epub 2011 Apr 13.
Insulin-like growth factor-binding protein 7 (IGFBP7) functions in several cellular processes including proliferation, senescence and apoptosis. This study analyzed IGFBP7 function in hepatocellular carcinoma (HCC) cells by gene manipulation and investigated the prognostic significance of IGFBP7 expression in clinical HCC samples. In this study, we investigated changes in malignant potential such as cell growth and invasiveness in an HCC cell line, PLC/PRF/5, after transfection with shRNA against IGFBP7. The extent of apoptosis and cell cycle progression were examined after the transfection. The correlation between immunohistochemically determined IGFBP7 expression and long-term postoperative prognosis after curative resection was also investigated in clinical HCC specimens obtained from 104 patients. PLC/PRF/5 cells transfected with shRNA against IGFBP7 showed significantly more rapid growth and stronger invasiveness than control cells. Annexin V assays showed that the IGFBP7-depleted cells were significantly more resistant to apoptosis than the control cells, and showed decreased expression of cleaved caspase-3 and PARP. Cell cycle progression was more rapid in the IGFBP7-suppressed cells. In clinical HCC specimens, IGFBP7 expression was judged as positive in 67 patients (64.4%) and negative in the remaining 37 patients (35.6%). The IGFBP7 downregulation correlated significantly with poor postoperative prognosis, and IGFBP7 status was identified as an independent significant prognostic factor. Our results indicated that IGFBP7 expression correlated significantly with the malignant potential in HCC cells, suggesting that the expression could be a useful prognostic marker for HCC.
胰岛素样生长因子结合蛋白 7（IGFBP7）在多种细胞过程中发挥作用，包括增殖、衰老和凋亡。本研究通过基因操作分析了 IGFBP7 在肝细胞癌（HCC）细胞中的功能，并研究了 IGFBP7 表达在临床 HCC 样本中的预后意义。在这项研究中，我们研究了 HCC 细胞系 PLC/PRF/5 转染 IGFBP7 短发夹 RNA（shRNA）后恶性潜能的变化，如细胞生长和侵袭性。转染后还检查了细胞凋亡和细胞周期进程的程度。还在 104 例接受根治性切除术后的 HCC 患者的临床标本中，研究了免疫组织化学确定的 IGFBP7 表达与长期术后预后的相关性。转染 IGFBP7 shRNA 的 PLC/PRF/5 细胞的生长速度明显快于对照组，侵袭性也明显增强。Annexin V 检测显示，IGFBP7 耗竭细胞的凋亡明显比对照组更具抵抗力，且 cleaved caspase-3 和 PARP 的表达降低。IGFBP7 抑制的细胞周期进展更快。在临床 HCC 标本中，67 例（64.4%）患者的 IGFBP7 表达为阳性，37 例（35.6%）患者为阴性。IGFBP7 下调与术后不良预后显著相关，IGFBP7 状态被确定为独立的显著预后因素。我们的结果表明，IGFBP7 表达与 HCC 细胞的恶性潜能显著相关，提示 IGFBP7 的表达可能是 HCC 的一个有用的预后标志物。
