NADPH oxidase DUOX1 and DUOX2 but not NOX4 are independent predictors in hepatocellular carcinoma after hepatectomy

Tumour Biol. 2011 Dec;32(6):1173-82. doi: 10.1007/s13277-011-0220-3. Epub 2011 Sep 14.

Abstract

NADPH oxidase DUOX1, DUOX2, and NOX4 have recently been gained considerable concerns, owing to the fact that they involve in reactive oxygen species-induced genetic and epigenetic alternations of human carcinogenesis and serve as biomarkers in several cancers. Whether they predict survival in hepatocellular carcinoma (HCC) is still uncertain. Here, we detected the expressions of DUOX1, DUOX2, and NOX4 in one normal liver cell line, seven HCC cell lines, 30 non-cirrhotic normal liver tissues, and 107 paired HCC tissues using reverse transcription-polymerase chain reaction. The correlations of genes expression with prognoses were analyzed. DUOX1 was expressed at high levels in MHCC-97H and MHCC-97L, but at low levels in Bel-7402. In contrast to low expression level at SMMC-7721, DUOX2 was expressed at considerably high levels in MHCC-97H and MHCC-97L. The transcript of NOX4 was only detected in SMMC-7721. All the 30 normal liver tissues failed to express the three candidate markers. Compared with adjacent non-neoplastic tissues, DUOX1, DUOX2, and NOX4 were expressed at higher frequencies in tumor specimens. Both univariate and multivariate analyses revealed that elevated expression of DUOX1 or DUOX2 predicted poorer recurrence-free survival and overall survival. No such significance trend regarding NOX4 predictive value in survival, however, was seen in univariate analysis. These results suggested DUOX1 and DUOX2, but not NOX4, could predict HCC prognoses after hepatectomy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery
  • Cell Line, Tumor
  • Dual Oxidases
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hepatectomy
  • Humans
  • Kaplan-Meier Estimate
  • Liver / enzymology
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Multivariate Analysis
  • NADPH Oxidase 4
  • NADPH Oxidases / genetics*
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult

Substances

  • Dual Oxidases
  • NADPH Oxidase 4
  • NADPH Oxidases
  • NOX4 protein, human
  • DUOX1 protein, human
  • DUOX2 protein, human