Huang Xiu-Yan, Huang Zi-Li, Tang Zhao-You, Xu Bin, Zheng Qi, Zhou Jian, Wang Lu, Ye Sheng-Long
Department of General Surgery, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
Zhonghua Yi Xue Za Zhi. 2010 May 11;90(18):1278-82.
To investigate the effects of palliative liver resection on metastatic potential and its gene function net of residual hepatocellular carcinoma (HCC) in nude mice model.
Orthotopic HCC model was established by implantation of human HCC cell line MHCC97H xenografts with a high metastatic potential. Thirty-six HCC-bearing nude mice were randomized into 3 groups at 14 days post-operation, including palliative resection group (HCC samples A, B), control group 1 (sham operation, HCC sample C1) and control group 2 (without intervention, HCC sample C2). Six mice in each group were sacrificed by cervical dislocation at 14 days after palliative resection. Oligo tumor metastasis microarray and GEArray expression analysis suite software were employed for gene analysis. The methods of support vector machine (SVM), gene significance analysis and gene correlation degree analysis were used to search the markers capable of differentiating the metastatic potential of HCC. Gene function net was constructed based on special gene clustering analysis and multi-dimensional scale. Real-time PCR was applied to detect the mRNA expression. The remaining mice were sacrificed at 35 days after palliative resection for the examination of pulmonary metastasis. SAS 8.2 software was used for statistical analysis.
Gene analysis showed that for different gene expression among groups, the density of gene net in palliative group (B, 0.0670) were higher than those in control groups (A, 0.0145; C1, 0.0210; C2, 0.0146), the condensation degree of gene net in residual HCC (B, 0.1940) was higher than that in its own control group (A, 0.0098). Human gene metastasis suppressor 1 (MTSS1) that encodes a protein of missing in metastasis B (MIM-B) was situated in the central position of gene function net of residual HCC. The relative MIM-B mRNA expression examined by Real-time PCR was significantly up-regulated in residual HCC (B, 0.283 +/- 0.023) as comparison was made among groups (A, 0.142 +/- 0.018; C1, 0.177 +/- 0.054; C2, 0.156 +/- 0.017, all P < 0.05). The number of lung metastatic nodules in the palliative group (14.3 +/- 4.7) was more than that in the sham group (8.7 +/- 3.6) at 35 days post-resection (P < 0.01).
Palliative liver resection enhances the pulmonary metastatic potential of residual HCC in nude mice model. MIM-B may be one of the key therapeutic targets for HCC patients.
在裸鼠模型中研究姑息性肝切除对残余肝细胞癌（HCC）转移潜能及其基因功能网络的影响。
通过植入具有高转移潜能的人HCC细胞系MHCC97H异种移植物建立原位HCC模型。术后14天，将36只荷HCC裸鼠随机分为3组，包括姑息性切除组（HCC样本A、B）、对照组1（假手术，HCC样本C1）和对照组2（未干预，HCC样本C2）。姑息性切除术后14天，每组处死6只小鼠，采用寡核苷酸肿瘤转移微阵列和GEArray表达分析套件软件进行基因分析。使用支持向量机（SVM）、基因显著性分析和基因相关度分析方法寻找能够区分HCC转移潜能的标志物。基于特殊基因聚类分析和多维尺度构建基因功能网络。应用实时PCR检测mRNA表达。其余小鼠在姑息性切除术后35天处死，检查肺转移情况。采用SAS 8.2软件进行统计分析。
基因分析显示，各组间基因表达不同，姑息性切除组（B，0.0670）的基因网络密度高于对照组（A，0.0145；C1，0.0210；C2，0.0146），残余HCC（B，0.1940）的基因网络凝聚度高于其自身对照组（A，0.0098）。编码转移缺失蛋白B（MIM-B）的人基因转移抑制因子1（MTSS1）位于残余HCC基因功能网络的中心位置。通过实时PCR检测，残余HCC中相对MIM-B mRNA表达显著上调（B，0.283±0.023），组间比较（A，0.142±0.018；C1，0.177±0.054；C2，0.156±0.017，均P<0.05）。切除术后35天，姑息性切除组的肺转移结节数（14.3±4.7）多于假手术组（8.7±3.6）（P<0.01）。
在裸鼠模型中，姑息性肝切除增强了残余HCC的肺转移潜能。MIM-B可能是HCC患者关键的治疗靶点之一。
