Prognostic impact of 8-hydroxy-deoxyguanosine and its repair enzyme 8-hydroxy-deoxyguanosine DNA glycosylase in hepatocellular carcinoma

Pathol Int. 2020 Aug;70(8):533-541. doi: 10.1111/pin.12952. Epub 2020 May 17.

Abstract

Hepatocellular carcinoma (HCC) has a poor prognosis in the setting of chronic inflammation and fibrosis, both of which promote nuclear DNA oxidative damage. 8-hydroxy-deoxyguanosine (8-OHdG) DNA glycosylase (OGG1) enhances the repair of 8-OHdG, which is the primary oxidative stress-induced mutation that leads to malignant alterations. This study aims to clarify the relationships between oxidative stress-induced factors and HCC progression. The clinicopathological factors were compared with immunohistochemistry OGG1 and 8-OHdG expressions in 86 resected HCC specimens. High 8-OHdG expression was associated with high serum aspartate transaminase and total bilirubin levels, as well as a low platelet count, compared with low 8-OHdG expression. Histological liver cirrhosis and poor differentiation were more frequent in patients with high 8-OHdG expression than in those with low 8-OHdG expression. The 8-OHdG was negatively correlated with OGG1 expression in HCC patients. Therefore, we classified the patients into two groups, low OGG1/high 8-OHdG group and the other group. The patients with low OGG1/high 8-OHdG expressions had worse prognosis than those with the other expressions. Our results showed that low OGG1/high 8-OHdG expressions in nuclei influence HCC patient outcomes. Evaluating the patterns of OGG1 and 8-OHdG expressions might provide pivotal prognostic biomarkers in patients with HCC.

Keywords: 8-hydroxy-deoxyguanosine; 8-hydroxy-deoxyguanosine DNA glycosylase; hepatocellular carcinoma; reactive oxygen species.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / pathology
  • DNA Glycosylases / metabolism*
  • Deoxyguanosine / metabolism
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Oxidative Stress
  • Prognosis
  • Reactive Oxygen Species / metabolism
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Reactive Oxygen Species
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA Glycosylases
  • Deoxyguanosine