Study of Dickkopf-1 (DKK-1) Gene Expression in Hepatocellular Carcinoma Patients

Introduction: Hepatocellular Carcinoma (HCC) is the sixth most common cancer in the world. Dickkopf -1 (DKK-1) protein is a new biomarker used in conjunction with Alpha Fetoprotein (AFP) to differentiate HCC from "non-malignant" liver disease. DKK-1 is an inhibitor of Wnt/β-catenin signaling pathway which is involved in embryogenesis and has been implicated in tumorigenesis in many tissues.

Aim: To investigate the level of DKK-1 gene expression in the peripheral blood of patients with HCC who had a history of Hepatitis C Virus (HCV) and schistosomal infections.

Materials And Methods: This "cross-sectional" study was carried out in the Tropical Medicine Department of Tanta University Hospital on 50 patients with HCC and 10 healthy volunteers served as control. All patients were tested for HCV antibodies and "anti-schistosomal" antibodies. All groups were tested for DKK-1 gene expression which was measured with quantitative real-time PCR.

Results: DKK-1 gene was over-expressed in HCC patients than in the control group with mean 3.269±4.762 versus 1.00 in controls (p< 0.005). "Over- expression" of DKK-1 was found in: 8/20 of patients with negative serology for both infections (40%; p<0.001), 7/18 of patients with positive anti-HCV antibodies (38.89%; p<0.001) and 11/12 of patients with positive anti-schistosomal antibodies (91.66%; p<0.001). There was no statistically significant correlation between DKK-1 expression and HCV infection (p=0.139) but there was significant correlation between the gene expression and schistosomal infection (p<0.001).

Conclusion: These data suggest the role of DKK-1 over-expression in HCC development in patients with combined HCV and schistosomal infections and that induction of the Wnt pathway or using DKK-1 antagonist may represent a key advance in the area of genetic prevention of HCC in these "high-risk" patients.