Establishment of metastatic molecule diagnostic model for hepatocellular carcinoma

Abstract

Listen

Translate article

Objective To construct the molecular model and screen the key molecules for evaluation of tumor metastatic potential in nude mice bearing hepatocellular carcinoma (HCC) xenografts.Methods Orthotopic HCC models were established by implantation of human HCC cell line MHCC97H xenografts with high metastatic potential.Thirty-six nude mice bearing HCC were randomized into three groups 14 days post-operation,including palliative resection group (samples A,B),sham operation group (sample C1),and control group (sample C2).Six mice in each group were sacrificed by cervical dislocation 14 days after palliative resection.Oligo Tumor Metastasis Microarray (OHS-028) and GEArray Expression Analysis Suite software were adopted for gene analysis.The methods of support vector machine (SVM),gene significance analysis and gene correlation degree analysis were used to find the markers that could differentiate the metastatic potential of HCC.Gene function net was constructed based on the special gene clustering analysis and multi-dimensional scale.The relevance vector machine (RVM) was used to deal with regression and classification problems.Real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) was applied to detect mRNA expression.Results By the method of support vector machine (SVM),we found the markers composed of 12 genes (BAI1,MTA2,MTA1,SMAD2,GNRH1,CDHS,ITGB3,CHD4,GZMA,ITGA7,CXCR4,and TSHR) could differentiate the metastatic potential of HCC with positive predictive rate of 88.9％ and 93.5％ in the groups with high and low metastatic potential respectively.In addition,it was found that MTSS1,transforming growth factor-β1 (TGF-β1),SMAD2,interleukin-1 β (IL-1 β) and matrix metalloproteinase-7 (MMP-7) were situated in the central position of the gene function net with high metastatic potential,which was confirmed by Real-time PCR.Conclusion The constructed molecule diagnostic model and the key molecules may be used to evaluate metastatic potential of HCC. Key words: Carcinoma, hepatocellular ; Molecular model; Invasion ; Metastasis