Predictive role BLVRA mRNA expression in hepatocellular cancer

Ann Hepatol. 2016;15(6):881-887. doi: 10.5604/16652681.1222104.

Abstract

Introduction and aim. Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. It is primarily caused by hepatic cirrhosis or chronic viral hepatitis. Hepatic carcinogenesis is associated with increased oxidative stress. Thus, the aim of our study was to assess expression of the genes involved in the homeostasis of oxidative stress in patients with HCC.

Material and methods: The study was performed on 32 patients with primary HCC (verified by liver histology in 29 patients) and 27 control subjects (in 11 subjects, liver histology was available either with no or minimal changes in the liver tissue). Gene expressions of heme oxygenase 1 (HMOX1), biliverdin reductase A/B (BLVRA/B), NADPH oxidase 2 (NOX2) and p22phox were analyzed in the liver and peripheral blood leukocytes (PBL) in the subjects.

Results: Compared to controls, almost a 3 times higher mRNA level of BLVRA was detected in livers of HCC patients (p = 0.002); while those of BLVRB as well as HMOX1 were unchanged (p > 0.05). In accord with these results in the liver tissue, BLVRA mRNA levels in PBL were also significantly increased in HCC patients (p = 0.012). mRNA levels of NOX2 and p22phox in the liver tissue, although higher in HCC patients, did not differ significantly compared to control subjects (p > 0.05). Nevertheless, NOX2 mRNA level in PBL was significantly higher in HCC patients (p = 0.003).

Conclusions: BLVRA mRNA levels in the liver as well as in PBL are significantly higher in HCC patients most likely as a feedback mechanism to control increased oxidative stress associated with HCC progression.

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Case-Control Studies
  • Disease Progression
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Heme Oxygenase-1 / genetics
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Membrane Glycoproteins / genetics
  • Middle Aged
  • NADPH Oxidase 2
  • NADPH Oxidases / genetics
  • Oxidative Stress / genetics
  • Oxidoreductases Acting on CH-CH Group Donors / blood
  • Oxidoreductases Acting on CH-CH Group Donors / genetics*
  • RNA, Messenger / genetics*
  • Signal Transduction
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Membrane Glycoproteins
  • RNA, Messenger
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Oxidoreductases Acting on CH-CH Group Donors
  • biliverdin reductase
  • CYBB protein, human
  • NADPH Oxidase 2
  • NADPH Oxidases
  • CYBA protein, human