title: Dickkopf-1: as a diagnostic and prognostic serum marker for early hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our data show that Dkk-1 is a diagnostic and prognostic serologic marker for early HCC.
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan - China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Fang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Stephanie Hiu Yan
authors.initials: SH
authors.lastname: Lau
authors.forename: Jin-Fan
authors.initials: JF
authors.lastname: Zhang
authors.forename: Wan Yee
authors.initials: WY
authors.lastname: Lau
authors.forename: Lian-Yue
authors.initials: LY
authors.lastname: Yang
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000509:alpha-Fetoproteins