Prognostic significance of death-associated protein-kinase expression in hepatocellular carcinomas

Disorder of programmed cell death (PCD) contributes to the pathogenesis and the progression of various cancers. Death-associated protein-kinase(DAP-kinase) was isolated as a positive mediator of apoptosis induced by IFN-gamma. It has been reported that the loss or reduction of DAP-kinase expression was detected in various human tumor cell lines and resulted from methylation of the DAP-kinase gene.

We investigated the expression of DAP-kinase protein by immunohistochemistry and Western-blotting in 43 patients with hepatocellular carcinoma (HCC). Additionally, we examined the methylation status of the DAP-kinase promoter region by methylation-specific polymerase chain reaction.

In DAP-kinase-positive HCC cases(n = 16), serum AFP levels were lower (p = 0.009), tumor differentiation was higher (p = 0.048), histological portal invasion and metastatic foci were less (p = 0.004 and 0.016, respectively), apoptosis of tumor cells was more (p = 0.0009), and the disease-free survival rate and the overall survival rate were higher (p = 0.0057 and 0.0246, respectively), compared with DAP-kinase-negative cases. The status of DAP-kinase protein expression closely correlated with IFN-gamma-receptor and Fas expression (p = 0.038 and p < 0.0001, respectively), but not the methylation of promoter region.

Hepatoma cells may escape from apoptosis through the loss or reduction of DAP-kinase expression, while the block of IFN-gamma signal transduction as well as the methylation of promoter region may reduce the expression of DAP-kinase protein.