Dickkopf-1: As a Diagnostic and Prognostic Serum Marker for Early Hepatocellular Carcinoma

Abstract

The aim of the present study was to evaluate serum Dickkopf-1 (Dkk-1) as a marker for early detection of hepatocellular carcinoma (HCC), as well as for prognostic prediction of early HCC after hepatic resection. One-hundred and four cases of matched fresh tissue specimens of early HCC and adjacent non-tumorous liver tissue (ANLT) were obtained for RT-PCR, qRT-PCR, western blot and immunohistochemistry assays. Sera were collected from patients with early HCC (n=184), benign liver tumors (n=29), cirrhosis (n=174), non-cirrhotic hepatitis B (n=193), and from healthy individuals (n=202). The levels of Dkk-1 and alpha fetoprotein (AFP) were measured. The Dkk-1 mRNA and protein levels were both upregulated in early HCC. Serum levels of Dkk-1 in patients with early HCC were significantly higher than in the other 4 groups (p<0.001). Dkk-1 had a better sensitivity and accuracy than AFP (p<0.05). More importantly, 73.1% of the patients negative for AFP could be diagnosed with early HCC using Dkk-1. A combination of Dkk-1 and AFP further improved the diagnostic efficacy. Patients with a high serum Dkk-1 level had poorer overall and relapse-free survivals than those with a low Dkk-1 level (p=0.028 and p=0.045, respectively). These results were shown in a testing cohort and confirmed in a validation cohort of patients. Univariable and multivariable Cox regression analyses showed serum Dkk-1 level to be an independent prognostic factor for overall survival. Our data show that Dkk-1 is a diagnostic and prognostic serologic marker for early HCC.