Impact of aldo-keto reductase family 1 member B10 on the risk of hepatitis C virus-related hepatocellular carcinoma.

Abstract

BACKGROUND AND AIM:

Aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was recently reported to be upregulated in some chronic liver diseases. However, its relevance in hepatocellular carcinoma (HCC) development is not fully assessed, especially in patients with chronic hepatitis C virus (HCV) infection.

METHODS:

Aldo-keto reductase family 1 member B10 expression in the liver of 550 patients with chronic HCV infection was immunohistochemically assessed and quantified. A multivariate Cox model was used to estimate the hazard ratios (HRs) of AKR1B10 expression for HCC development, and the cumulative incidence of HCC was evaluated using the Kaplan-Meier method.

RESULTS:

Aldo-keto reductase family 1 member B10 expression in the patients ranged from 0% to 80%. During the median follow-up of 3.2 years, 43 of 550 patients developed HCC. Multivariate analysis demonstrated that high AKR1B10 expression (≥6%) was an independent risk factor for HCC (HR, 6.43; 95% confidence interval, 2.90-14.25; P < 0.001). The 5-year cumulative incidences of HCC were 22.8% and 2.2% in patients with high and low AKR1B10 expression, respectively (P < 0.001). In subgroup analyses, the effects of high AKR1B10 expression on HCC development risk were significant over strata. In particular, HRs attributed to high AKR1B10 expression were significant in the subgroups that had been considered at a lower risk of HCC, such as in patients with younger age and mild hepatic fibrosis or those who achieved sustained virological response after interferon therapy.

CONCLUSION:

Various degrees of AKR1B10 upregulation in the liver were observed in patients with chronic HCV infection, and high AKR1B10 expression could be a novel predictor of HCC.

• Authors: Shunsuke Sato, Takuya Genda, Takafumi Ichida, Ayato Murata, Hironori Tsuzura, Yutaka Narita, Yoshio Kanemitsu, Sachiko Ishikawa, Tetsu Kikuchi, Masashi Mori, Katsuharu Hirano, Katsuyori Iijima, Ryo Wada, Akihito Nagahara, Sumio Watanabe
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 31 Issue 7 Pg. 1315-22 (Jul 2016) ISSN: 1440-1746 [Electronic] Australia
• PMID: 26758591 (Publication Type: Journal Article)
• Copyright: © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• AKR1B10 protein, human
• Aldo-Keto Reductases
• Aldehyde Reductase

Topics

• Adult
• Aged
• Aged, 80 and over
• Aldehyde Reductase (genetics, metabolism)
• Aldo-Keto Reductases
• Carcinoma, Hepatocellular (enzymology, epidemiology, genetics)
• Gene Expression
• Hepatitis C, Chronic (enzymology, genetics)
• Humans
• Immunohistochemistry
• Incidence
• Kaplan-Meier Estimate
• Liver (enzymology)
• Liver Neoplasms (enzymology, epidemiology, genetics)
• Middle Aged
• Predictive Value of Tests
• Proportional Hazards Models
• Risk
• Up-Regulation (genetics)