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.
Keywords: AKR1B10; HSP70; glypican-3; hepatocellular carcinoma; chronic hepatitis; cirrhosis
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Tsuzura, H.; Genda, T.; Sato, S.; Murata, A.; Kanemitsu, Y.; Narita, Y.; Ishikawa, S.; Kikuchi, T.; Mori, M.; Hirano, K.; Iijima, K.; Wada, R.; Ichida, T. Expression of Aldo-Keto Reductase Family 1 Member B10 in the Early Stages of Human Hepatocarcinogenesis. Int. J. Mol. Sci. 2014, 15, 6556-6568.
Tsuzura H, Genda T, Sato S, Murata A, Kanemitsu Y, Narita Y, Ishikawa S, Kikuchi T, Mori M, Hirano K, Iijima K, Wada R, Ichida T. Expression of Aldo-Keto Reductase Family 1 Member B10 in the Early Stages of Human Hepatocarcinogenesis. International Journal of Molecular Sciences. 2014; 15(4):6556-6568.
Tsuzura, Hironori; Genda, Takuya; Sato, Shunsuke; Murata, Ayato; Kanemitsu, Yoshio; Narita, Yutaka; Ishikawa, Sachiko; Kikuchi, Tetsu; Mori, Masashi; Hirano, Katsuharu; Iijima, Katsuyori; Wada, Ryo; Ichida, Takafumi. 2014. "Expression of Aldo-Keto Reductase Family 1 Member B10 in the Early Stages of Human Hepatocarcinogenesis." Int. J. Mol. Sci. 15, no. 4: 6556-6568.