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


ABSTRACT: 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 ng/mL) and normal AFP (<10 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 < 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 (>6%) was an independent risk factor for HCC development (hazard ratio, 21.4; P = 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.

SUBMITTER: Sato S 

PROVIDER: S-EPMC3466415 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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

Sato Shunsuke S   Genda Takuya T   Hirano Katsuharu K   Tsuzura Hironori H   Narita Yutaka Y   Kanemitsu Yoshio Y   Kikuchi Tetsu T   Iijima Katsuyori K   Wada Ryo R   Ichida Takafumi T  

Liver international : official journal of the International Association for the Study of the Liver 20120611 9


<h4>Background</h4>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.<h4>Aim</h4>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.<h4>Methods</h4>Liver tissue samples from 48 chronic hepatitis C patients were stratified by their serum AFP levels and analysed for g  ...[more]

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