Two candidate genes for liver carcinogenesis identified in tree shrews and humans

Li Y et al. (2008) Candidate genes responsible for human hepatocellular carcinoma identified from differentially expressed genes in hepatocarcinogenesis of the tree shrew (Tupaia belangeri chinensis). Hepatol Res 38: 85–95

Numerous genes have been identified that might contribute to the development of hepatocellular carcinoma (HCC); however, the genes most important in liver carcinogenesis are not yet known. Li and colleagues identified differentially expressed genes in an animal model of HCC, and compared these findings with those obtained in human HCC.

HCC was induced in tree shrews (Tupaia belangeri chinensis), which have a closer evolutionary relationship with humans than do other commonly used rodent species, by exposure to either aflatoxin B₁ (AFB₁) or HBV plus AFB₁. Biopsy samples of HCC tissue, HCC-surrounding tissue (para-HCC) and liver tissue before HCC onset (pre-HCC) were analyzed by cDNA microarray assay. This analysis highlighted 11 genes that showed altered expression patterns in both AFB₁-induced and AFB₁ + HBV-induced HCC. Two genes, SOD1, which encodes an antioxidant enzyme, and GSTA1, which encodes an apoptosis-associated protein, were downregulated in HCC tissue compared to para-HCC and pre-HCC tissue.

Reverse-transcriptase polymerase chain reaction and immunohistochemical assays showed that SOD1 and GSTA1 mRNA and protein levels were also significantly downregulated in human HCC samples, and levels of both proteins also inversely correlated with histopathological tumor grade (all P <0.05).

The authors conclude that SOD1 and GSTA1 seem to be differentially expressed in all cases of HCC regardless of etiology, and of the species in which HCC occurs. These genes should, therefore, be studied further as potential key mediators in liver carcinogenesis.