Abstract:
Objective To analyze the expression and subcellular localization of Wnt antagonist Dickkopf-3 (DKK3) in hepatocellular carcinoma (HCC) and to investigate the clinical implication of DKK3 expression in HCC.
Methods DKK3 protein expression in the liver cancer cell line, 43 tissue samples of HCC and corresponding adjacent tissue, was examined with immunofluorescence or immunohistochemistry. The DKK3 methylation status was then assayed by methylation-specific PCR in 31 cases of HCC and paired adjacent tissue.
Results High DKK3 protein expression level was observed in 67.4% (29 / 43) of HCC tissue, significantly higher than that in the paired adjacent tissue 41.8 % (18 / 43), P= 0.017, and DKK3 protein was mainly expressed in the cell nucleus. DKK3 gene methylation was detected in 90.3% (28/31) of HCC tissue samples, significantly higher than that in the corresponding adjacent tissue samples 64.5 % (20 / 31), P= 0.015. No correlation was found between DKK3 methylation status and its protein expression (P= 0.844). Patients with low DKK3 expression had higher overall or disease-free survival than those with high expression of this protein (P= 0.049, 0.001).
Conclusion No correlation exists between the DKK3 methylation status and its protein expression. High DKK3 expression may promote HCC, and DKK3 protein expression in HCC tissue may be used as a prognostic marker for hepatocellular carcinoma.