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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
Author(s) -
Sato Shunsuke,
Genda Takuya,
Hirano Katsuharu,
Tsuzura Hironori,
Narita Yutaka,
Kanemitsu Yoshio,
Kikuchi Tetsu,
Iijima Katsuyori,
Wada Ryo,
Ichida Takafumi
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2012.02827.x
Subject(s) - hepatocellular carcinoma , alpha fetoprotein , immunohistochemistry , medicine , real time polymerase chain reaction , gastroenterology , gene , pathology , biology , biochemistry
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 ( AKR 1B10) expression and serum AFP was confirmed by quantitative real‐time reverse transcription polymerase chain reaction (q RT ‐ PCR ) and immunohistochemical analyses. A matched case‐control study was performed to evaluate the risk of AKR 1B10 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 AKR 1B10 (fold change, 26.2; P < 0.001), which was originally isolated as an overexpressed gene in human HCC . The q RT ‐ PCR and immunohistochemical studies confirmed a proportional correlation between AKR 1B10 expression and serum AFP . A matched case‐control study identified that AKR 1B10 up‐regulation (>6%) was an independent risk factor for HCC development (hazard ratio, 21.4; P = 0.001). Conclusion AKR 1B10 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.