High expression of AKR1B10 predicts low risk of early tumor recurrence in patients with hepatitis B virus-related hepatocellular carcinoma

Yan-Yan Wang,Bang-De Xiang,Liang Ma,Jia-Zhou Ye,Shi-Dong Lu,Jian-Hong Zhong,Le-Qun Li,Hong-Gui Qin,Xue-Mei You,Lu-Nan Qi

doi:10.1038/srep42199

Abstract

To clarify the relationship between aldo-keto reductase family 1 member B10 (AKR1B10) expression and early hepatocellular carcinoma (HCC) recurrence, this study detected AKR1B10 expression in tumor and adjacent non-tumor tissues from 110 patients with hepatitis B virus (HBV)-related HCC underwent liver resection and analyzed its correlations with clinicopathological characteristics and prognosis of these patients. Detected by quantitative reverse transcription polymerase chain reaction, AKR1B10 mRNA expression showed significantly higher in HCC tissues than in adjacent non-tumor tissues, with a low level in normal liver tissues. Similar results was confirmed at the protein level using immunohistochemistry and Western blotting. High AKR1B10 expression was negatively correlated with serum alpha-fetoprotein level and positively correlated with HBV-DNA level. Patients with high AKR1B10 expression had significantly higher disease-free survival than those with low expression within 2 years after liver resection. Multivariate analysis also confirmed high AKR1B10 expression to be a predictor of low risk of early HCC recurrence. In addition, high AKR1B10 expression was found to be a favorable factor of overall survival. These results suggest that AKR1B10 is involved in HBV-related hepatocarcinogenesis, but its high expression could predict low risk of early tumor recurrence in patients with HBV-related HCC after liver resection.

Highlights

Heringlake et al.[18] identified AKR1B10 as an overexpressed gene in Hepatocellular carcinoma (HCC), and our laboratory has associated HCC with elevated AKR1B10 protein using quantitative proteomics[19]
Survival analysis showed that high expression of AKR1B10 was a predictor for low risk of early tumor recurrence in patients with hepatitis B virus (HBV)-related HCC after liver resection
Using quantitative reverse transcription polymerase chain reaction (qRT-PCR), we found levels of AKR1B10 mRNA to be significantly higher in HBV-related HCC tissues than in adjacent non-tumor tissues, and we found that levels were higher in the adjacent non-tumor tissues from HCC patients than in normal liver tissues from patients with hepatic hemangioma without HBV or hepatitis C virus (HCV) infection

Summary

Introduction

Heringlake et al.[18] identified AKR1B10 as an overexpressed gene in HCC, and our laboratory has associated HCC with elevated AKR1B10 protein using quantitative proteomics[19] These findings indicate that AKR1B10 may be involved in hepatocarcinogenesis. Jin et al.[21] associated high expression of AKR1B10 mRNA with poor disease-free survival (DFS) and overall survival (OS) in patients with HCC These two studies reported substantially different patterns of AKR1B10 expression in patients with HCC in different stages. Given these discrepancies and the fact that the patient populations in both studies were heterogeneous in terms of HCC risk factors, the possible relationship between AKR1B10 expression and early HCC recurrence remains unclear. The impact of AKR1B10 expression on HBV-related hepatocarcinogenesis was evaluated

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