Differentially expressed genes in hepatocellular carcinoma of tree shrew induced by different factors

BACKGROUND & OBJECTIVE: Previous studies on differentially expressed genes in hepatocellular carcinoma (HCC) used to perform with para-cancerous tissues as normal control. However, the para-cancerous tissue of HCC is actually abnormal because they frequently contain hepatitis, cirrhosis, hyperplastic nodules or foci, etc. In order to explore the molecular mechanism and the responsible genes for hepatocarcinogenesis, through applying the HCC model of tree shrew (Tupaia belangeri chinensis), this study was designed to compare gene expression levels between HCC induced by different factors and their corresponding biopsies taken before HCC formation. METHODS: Tree shrews were divided into two groups. Group AFB(1) was fed with aflatoxin B1 (AFB(1)). Group AFB(1)+HBV was infected firstly with human hepatitis B virus (HBV) and then fed with AFB(1) as group AFB(1). Serum tests for HBV markers and liver biopsies were performed periodically during the experiment. After appearance of HCC, 2 HCC samples from each group and their corresponding 30th-week biopsies were tested respectively by cDNA microarray assay. The gene expression levels were compared between each HCC and the corresponding biopsies, and the differentially expressed genes from the two groups of HCC induced by different factors were analyzed. RESULTS: The incidence rates of HCC in group AFB(1) and group AFB(1)+HBV were 73.3% and 77.8%, respectively. A considerable number of genes in both groups showed changes in their expression levels, which were mainly up-regulated in group AFB(1) but down-regulated in group AFB(1)+HBV. On the other hand, among the 588 checked genes (16 functional classifications) that were known related to human cancer, 11 genes were similarly expressed in all of the 4 HCC from the two animal groups. Most of these 11 genes belonged functionally to 3 types, namely "apoptosis-associated protein","DNA synthesis,repair and recombination proteins", and "growth factors, cytokines and chemokines". CONCLUSION: (1)HBV can affect AFB(1)-induced gene expression in certain extent. (2)The gene expression profiles of HCC induced by different factors are different. (3)The common differentially expressed genes in these two HCC groups are worthwhile for further study as the possibly responsible genes for hepatocarcinogenesis.