Up-regulated aldo-keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha-fetoprotein and hepatocellular carcinoma

作者：Sato Shunsuke; Genda Takuya^*; Hirano Katsuharu; Tsuzura Hironori; Narita Yutaka; Kanemitsu Yoshio; Kikuchi Tetsu; Iijima Katsuyori; Wada Ryo; Ichida Takafumi

来源：Liver International, 2012, 32(9): 1382-1390.

DOI：10.1111/j.1478-3231.2012.02827.x

• AKR1B10
• alpha-fetoprotein
• carcinogenesis
• chronic hepatitis C
• liver
• microarray
• risk factor

Background Elevated serum alpha-fetoprotein (AFP) is not only a diagnostic marker for hepatocellular carcinoma (HCC), but is also a risk factor for HCC in chronic hepatitis C patients who do not have HCC. Aim The aim was to analyse the hepatic gene expression signature in chronic hepatitis C patients with elevated AFP, who were at high risk for HCC. Methods Liver tissue samples from 48 chronic hepatitis C patients were stratified by their serum AFP levels and analysed for gene expression profiles. The association between aldo-keto reductase family 1 member B10 (AKR1B10) expression and serum AFP was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analyses. A matched case-control study was performed to evaluate the risk of AKR1B10 expression for HCC development. Results Distinct hepatic gene expression patterns were demonstrated in patients with elevated AFP (=10 similar to ng/mL) and normal AFP (%26lt;10 similar to ng/mL). Of the 627 differently expressed genes, the most abundantly expressed gene in patients with elevated AFP was AKR1B10 (fold change, 26.2; P similar to%26lt;similar to 0.001), which was originally isolated as an overexpressed gene in human HCC. The qRT-PCR and immunohistochemical studies confirmed a proportional correlation between AKR1B10 expression and serum AFP. A matched case-control study identified that AKR1B10 up-regulation (%26gt;6%) was an independent risk factor for HCC development (hazard ratio, 21.4; P similar to=similar to 0.001). Conclusion AKR1B10 was up-regulated in association with serum AFP, and was an independent risk factor for HCC in chronic hepatitis C patients, suggesting its possible involvement at a very early stage of hepatocarcinogenesis.

• 出版日期2012-10