Functional analysis of differentially expressed genes in hepatic stem cells and the application to the diagnosis of chronic hepatitis and liver cirrhosis.

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We have demonstrated for the first time that APP and DKK-3 are differentially expressed in adult HSLCs. The expression of APP and DKK-3 in the liver was characteristically higher at a very early fetal stage than in the intermediate or late stage, or in adult liver, and was inversely correlated with the expression of AFP and ALB. Moreover, DKK-3, like AFP, was up-regulated in 7D liver of 80% HM. Both 5^<th> GW fetal liver and 7D liver of 80% HM were shown to be proliferating and to have similar developing histology. Cells expressing DKK-3 were located in the hepatic parenchyma of 5^<th> GW fetal liver, and in the periportal area of normal and regenerating adult liver, suggesting the possible presence of adult HSLCs in the periportal area. These results suggested that DKK-3 was up-regulated in immature and developing liver, and was possibly involved in hepatic differentiation and liver regeneration. Furthermore, to evaluate the relation between DKK-3 expression and hepatic differentiation in hepatoblastomas (HBLs) and hepatocellular carcinomas (HCCs) and the utility of DKK-3 as a diagnostic marker of these hepatic malignant tumors, we analyzed the expression pattern of DKK-3 in primary fourteen HBLs and seventy-two HCCs by in situ hybridization and IHC. Cases expressing DKK-3 were 79% in HBLs and 21% in HCCs. Cases co-expressing DKK-3 and alpha-fetoprotein (AFP) were 57% in HBLs and 10% in HCCs, and cases expressing DKK-3 or AFP were 100% in HBLs and 72% in HCCs. The results support the histological similarity of HBLs to embryonal or fetal liver rather than HCCs, and suggest that DKK-3 is a useful diagnostic marker of HBLs to detect the wide rage of HBLs.