N-myc downstream regulated gene 1 (NDRG1)/Cap43 enhances portal vein invasion and intrahepatic metastasis in human hepatocellular carcinoma

Oncol Rep. 2008 Dec;20(6):1329-35.


N-myc downstream regulated gene 1 (NDRG1)/Cap43 is a 43 kDa protein that is widely distributed in the body. Its expression is regulated by nickel, cobalt, hypoxic condition and others; it is reported to be weaker in tumors than normal tissues; and NDRG1/Cap43 is considered to act suppressively to tumor metastasis. This current study immunohistochemically examined NDRG1/Cap43 expression in hepatocellular carcinoma (HCC), and analyzed its relationship to clinicopathologic factors and prognosis. The samples were 105 surgically resected HCC tissue blocks, i.e., 18 well-differentiated HCC, 61 moderately differentiated HCC, 10 poorly differentiated HCC, 9 'nodule-in-nodule' type HCC, and 7 sarcomatous HCC. In all cases, NDRG1/Cap43 was not expressed in normal liver cells. Strong expression was found in 65 of the 105 cases (62%), i.e., in 11.1% of well-differentiated HCC, 72.1% of moderately differentiated HCC, 80.0% of poorly differentiated HCC, and 71.4% of sarcomatous HCC. In the 'nodule-in-nodule' type, its expression was found in 55.6% of their well-differentiated component, and this frequency was significantly higher than that in well-differentiated HCC (11.1%). In the cases showing strong NDRG1/Cap43 expression, frequency of portal vein invasion and of intrahepatic metastasis was significantly high. No clear relationship between the expression and prognosis was observed. NDRG1/Cap43 expression that was found in advanced HCC was thought to accelerate tumor invasion and metastasis. NDRG1/Cap43 could act as a useful biomarker of HCC.

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle Proteins / biosynthesis*
  • Cell Cycle Proteins / physiology*
  • Cell Differentiation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Liver / metabolism
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Portal Vein / pathology*
  • Prognosis


  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • N-myc downstream-regulated gene 1 protein