Experimental observation on the alteration of metastatic potential and its gene function net of residual hepatocellular carcinoma following palliative liver resection

Abstract

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.