Wilms' tumour 1 gene expression is increased in hepatocellular carcinoma and associated with poor prognosis

Eur J Cancer. 2008 Mar;44(4):600-8. doi: 10.1016/j.ejca.2008.01.008. Epub 2008 Feb 5.

Abstract

Background/aims: Wilms' tumour 1 gene (WT1) was originally isolated as a tumour-suppressor gene. We investigated the expression of WT1 in hepatocellular carcinoma (HCC; T) and in non-cancerous hepatic tissues (non-tumour: NT) from patients with chronic liver diseases, and then examined the role of WT1 in the carcinogenesis or prognosis of HCC.

Methods: The expression of WT1 in T and NT from 50 patients with HCC was investigated using Western blotting, immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). We also examined whether WT1 expression was related to clinicopathological factors in individual patients in addition to prognostic factors in 50 patients with HCC and in 26 without HCC.

Results: Western blotting and immunohistochemical staining showed that WT1 was overexpressed in T compared with NT (P<0.001) and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) showed that WT1 mRNA expression was similarly increased. Overexpressed WT1 in HCC was significantly associated with T factors at the TNM stage, and short doubling time of HCC. Univariate and multivariate analyses revealed that WT1 overexpression was an independent prognostic factor for HCC. The disease-free survival period in patients with overexpressed WT1 in NT tissues was significantly reduced.

Conclusion: The expression of WT1 is increased more in HCC than in non-tumour tissues. Moreover, overexpressed WT1 was associated with tumour growth, and resulted in a worsening prognosis of HCC. Our findings from NT tissues revealed that WT1 overexpression might contribute to oncogenic potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adult
  • Aged
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / mortality
  • Cell Cycle Proteins
  • Disease-Free Survival
  • Female
  • Genes, Wilms Tumor*
  • Humans
  • Immunohistochemistry
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / mortality
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Prognosis
  • RNA Splicing Factors
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Actins
  • Cell Cycle Proteins
  • Nuclear Proteins
  • RNA Splicing Factors
  • WTAP protein, human