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
Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan.
Department of Pathology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan.
Int J Mol Sci. 2014 Apr 17;15(4):6556-68. doi: 10.3390/ijms15046556.
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.
醛糖 - 酮糖还原酶家族1成员B10(AKR1B10)是一种与癌症相关的氧化还原酶,在高分化肝细胞癌(HCC)中表达。然而,AKR1B10在正常肝组织(NL)中的水平极低,类似于70千道尔顿热休克蛋白(HSP70)和磷脂酰肌醇蛋白聚糖 - 3。此外,AKR1B10在被认为是HCC癌前病变的慢性肝炎或肝硬化中的作用尚未完全阐明。本研究的目的是评估61例HCC组织样本中AKR1B10、HSP70和磷脂酰肌醇蛋白聚糖 - 3的表达,并与相应的非肿瘤性肝组织(NT)进行比较,NT包括42例慢性肝炎和19例肝硬化病例,以阐明HCC癌前阶段分子变化的意义。免疫组织化学分析表明,HCC中AKR1B10的中位表达水平高于NT(p<0.001),NT中高于NL(p<0.001),在HCC、NT和NL中的表达分别为54.8%、2.1%和0.3%。HSP70和磷脂酰肌醇蛋白聚糖 - 3在HCC中表达,但在NT和NL中表达极低,NT和NL之间的表达无显著差异。此外,多变量分析确定了肝脂肪变性与NT中AKR1B10表达之间存在关联(p = 0.020)。在高分化HCC中表达的三种蛋白质中,只有AKR1B10在癌前病变中上调,并且一个与脂肪变性相关的因素可能影响其表达。