title: Elevated expression of DKK1 is associated with cytoplasmic/nuclear beta-catenin accumulation and poor prognosis in hepatocellular carcinomas.
abstract: OBJECTIVE
  To assess the value of Dickkopf-1 (DKK1) for predicting clinical outcome of human hepatocellular carcinoma (HCC) in patients with HCC.
  
  
  METHODS
  Expression of DKK1 and beta-catenin was investigated in HCC cell lines using qRT-PCR, Western blotting and immunofluorescence. Tissue microarrays representing 314 HCC patients were used to determine the expression patterns of DKK1 and beta-catenin by immunohistochemistry, and prognostic significance was assessed by using Kaplan-Meier survival estimates and log-rank tests.
  
  
  RESULTS
  The expression level of DKK1 was associated with the staining pattern of beta-catenin in HCC cell lines, and DKK1 overexpression correlated with beta-catenin cytoplasmic/nuclear accumulation in clinical HCC samples (P=0.011, correlation coefficient=0.144). High DKK1 expression predicted unfavorable prognosis in HCC patients, especially in early stage patients and those with normal AFP levels. In multivariate analyses, DKK1 was an independent predictor for overall survival (OS) (P=0.002) and disease-free survival (DFS) (P=0.002) of HCC patients. Furthermore, the HCC patients with high DKK1 expression and cytoplasmic/nuclear beta-catenin accumulation had very poor prognosis.
  
  
  CONCLUSIONS
  Elevated expression of DKK1 is a critical event in patients with HCC that indicates poor clinical outcome. DKK1, alone or combined with beta-catenin, is a novel prognostic predictor for HCC patients.
authors.affiliation: Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Xinrong
authors.initials: X
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Genfu
authors.initials: G
authors.lastname: Yao
authors.forename: Huiqun
authors.initials: H
authors.lastname: Shu
authors.forename: Biaoyang
authors.initials: B
authors.lastname: Lin
authors.forename: Leroy
authors.initials: L
authors.lastname: Hood
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
authors.forename: Shengli
authors.initials: S
authors.lastname: Yang
authors.forename: Jianren
authors.initials: J
authors.lastname: Gu
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Wenxin
authors.initials: W
authors.lastname: Qin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C501126:DKK1 protein, human; D004273:DNA, Neoplasm; D036341:Intercellular Signaling Peptides and Proteins; D051176:beta Catenin