Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
Liver Int. 2012 Oct;32(9):1382-90. doi: 10.1111/j.1478-3231.2012.02827.x. Epub 2012 Jun 11.
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.
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.
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.
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).
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.
血清甲胎蛋白（AFP）升高不仅是肝细胞癌（HCC）的诊断标志物，也是无 HCC 的慢性丙型肝炎患者发生 HCC 的危险因素。
分析血清 AFP 升高、HCC 风险高的慢性丙型肝炎患者的肝基因表达谱。
根据血清 AFP 水平对 48 例慢性丙型肝炎患者的肝组织样本进行分层，并分析基因表达谱。通过定量实时逆转录聚合酶链反应（qRT-PCR）和免疫组织化学分析证实醛酮还原酶家族 1 成员 B10（AKR1B10）表达与血清 AFP 的关联。进行匹配的病例对照研究，以评估 AKR1B10 表达对 HCC 发展的风险。
在 AFP 升高（≥10ng/ml）和 AFP 正常（<10ng/ml）的患者中，显示出明显不同的肝基因表达模式。在 627 个差异表达基因中，血清 AFP 升高患者中表达最丰富的基因是 AKR1B10（倍数变化，26.2；P<0.001），这是最初在人类 HCC 中分离出来的过度表达基因。qRT-PCR 和免疫组织化学研究证实 AKR1B10 表达与血清 AFP 之间存在比例相关性。匹配的病例对照研究表明，AKR1B10 上调（>6%）是 HCC 发展的独立危险因素（危险比，21.4；P=0.001）。
AKR1B10 与血清 AFP 上调相关，是慢性丙型肝炎患者 HCC 的独立危险因素，提示其可能在肝癌发生的早期阶段发挥作用。
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