Comparative analysis of expression profiling of early-stage carcinogenesis using nodule-in-nodule-type hepatocellular carcinoma

BACKGROUNDNodule-in-nodule-type hepatocellular carcinoma (NIN-HCC) is a useful model to illustrate the multi-step nature of hepatocarcinogenesis. To identify large-scale molecular change in early hepatocarcinogenesis, the expression profile of NIN-HCC was compared with those from three sets of individual high-grade dysplastic nodules (HGDN) and grade 1 hepatocellular carcinomas. METHODSWe compared expression profiles of inner grade 1 hepatocellular carcinoma nodules and peripheral HGDN in one case of NIN-HCC using spotted-oligonucleotide DNA microarray. The relevant outlier genes assumed to associate with early carcinogenesis in hepatocellular carcinoma were identified by comparative analysis of NIN-HCC and individual cases of HGDN and grade 1 hepatocellular carcinoma, respectively. RESULTSFrom this analysis we extracted a total of 40 genes, consisting of 28 up-regulated genes and 12 downregulated genes, and more than a two-fold change in grade 1 hepatocellular carcinoma compared with HGDN. CONCLUSIONWe assessed the expression profiles of pre-neoplastic lesions and grade 1 hepatocellular carcinoma using oligonucleotide microarray analysis and found high stringent outlier genes that are presumably directly involved in the transition from dysplastic nodule to the early stage of hepatocellular carcinoma by utilizing NIN-HCC.