Expression of aldo-keto reductase family 1 member b10 in the early stages of human hepatocarcinogenesis.

Hironori Tsuzura,Masashi Mori,Katsuyori Iijima,Yutaka Narita,Katsuharu Hirano,Takafumi Ichida,Ayato Murata,Shunsuke Sato,Ryo Wada,Yoshio Kanemitsu,Takuya Genda,Sachiko Ishikawa,Tetsu Kikuchi

doi:10.3390/ijms15046556

Abstract

Aldo-keto reductase family 1, member B10 (AKR1B10), a cancer-related oxidoreductase, is expressed in well-differentiated hepatocellular carcinomas (HCCs). However, AKR1B10 levels are minimal in normal liver tissues (NLs), similar to the 70-kilodalton heat shock protein (HSP70) and glypican-3. Moreover, the role of AKR1B10 in chronic hepatitis or cirrhosis, which are considered preneoplastic conditions for HCC, has not been fully elucidated. The aim of this study was to evaluate the expression of AKR1B10, HSP70, and glypican-3 in 61 HCC tissue samples compared to corresponding non-tumorous liver tissues (NTs), comprising 42 chronic hepatitis and 19 cirrhosis cases to clarify the significance of molecular changes at the preneoplastic stages of HCC. Immunohistochemical analysis demonstrated that the median expression levels of AKR1B10 were higher in HCCs than in NTs (p < 0.001) and higher in NTs than NLs (p < 0.001) with 54.8%, 2.1%, and 0.3% expression in HCCs, NTs, and NLs, respectively. HSP70 and glypican-3 were expressed in HCCs, but minimally in NTs and NLs with no significant difference between expression in NTs and NLs. Furthermore, a multivariate analysis identified an association between hepatic steatosis and AKR1B10 expression in NTs (p = 0.020). Of the three protein expressed in well-differentiated HCCs, only AKR1B10 was upregulated in preneoplastic conditions, and a steatosis-related factor might influence its expression.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide [1]
The molecular alterations underlying preneoplastic conditions that predispose to HCC remain poorly understood
We analyzed the expression profiles of approximately 41,000 genes in patients with chronic hepatitis C and found that AKR1B10 was upregulated in the livers of chronic hepatitis C patients at high risk of HCC [13]. These observations suggest that an alteration of AKR1B10 expression occurs even in preneoplastic conditions that predispose to HCC

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide [1]. HCC is characterized by a multistep morphological developmental process, progressing from early, well-differentiated HCC to moderately or poorly differentiated, advanced HCC [2]. The majority of HCCs arise in chronically diseased livers, including livers with chronic hepatitis and cirrhosis resulting from hepatitis B or C infection or exposure to other carcinogenic factors. These chronic liver diseases are widely considered to be preneoplastic conditions for HCC, potentially leading to molecular alterations that predispose hepatocytes to malignant transformation. The molecular alterations underlying preneoplastic conditions that predispose to HCC remain poorly understood

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