Up-regulated aldo-ketoreductase1B10 in chronic hepatitis C: Association with serum alpha-fetoprotein and hepatocellular carcinoma. Homo sapiens

We attempted to identify a specific gene expression signature by performing microarray analysis on the livers of patients with chronic hepatitis C and AFP elevation. Distinct hepatic gene expression patterns were demonstrated between patients with elevated AFP (≥10ng/mL) and normal AFP (<10ng/mL). Among the 30,150 valid genes, 627 were identified as differentially expressed genes with a minimal fold change of 2.0. Using these 627 genes, PCA and HCA were used to successfully distinguish samples according to their AFP status. Of the 627 differently expressed genes, AKR1B10 was most abundantly expressed in patients with elevated AFP. AKR1B10 expression was validated by Real-time RT-PCR and immunohistochemical study. Furthermore, a proportional correlation between AKR1B10 expression and serum AFP was demonstrated by regression analysis. A matched case-control study indicated that AKR1B10 up-regulation was an independent risk factor for HCC development. Overall design: Liver tissues samples from 48 chronic hepatitis C patients were stratified by their serum AFP levels and analyzed for gene expression profiles. AKR1B10 was up-regulated in patients with chronic hepatitis C in association with serum AFP, and was an independent risk factor for HCC development.

我们通过对慢性丙型肝炎且甲胎蛋白（Alpha-fetoprotein, AFP）升高患者的肝脏组织开展基因微阵列分析，旨在鉴定特异性基因表达特征。结果显示，甲胎蛋白升高组（≥10ng/mL）与甲胎蛋白正常组（<10ng/mL）患者的肝脏基因表达模式存在显著差异。在30150个有效基因中，共筛选得到627个差异表达基因，其最小表达倍数变化为2.0。利用这627个差异基因，通过主成分分析（Principal Component Analysis, PCA）与层次聚类分析（Hierarchical Cluster Analysis, HCA），可依据样本的甲胎蛋白状态实现有效区分。在上述627个差异表达基因中，AKR1B10在甲胎蛋白升高患者中的表达丰度最高。该基因的表达水平经实时逆转录聚合酶链反应（Real-time RT-PCR）与免疫组化实验验证。此外，回归分析证实AKR1B10的表达水平与血清甲胎蛋白水平呈正相关。一项匹配病例对照研究显示，AKR1B10基因上调是肝细胞癌（Hepatocellular carcinoma, HCC）发生的独立危险因素。
Overall design: 本研究纳入48例慢性丙型肝炎患者的肝脏组织样本，按其血清甲胎蛋白水平进行分层，并开展基因表达谱分析。
慢性丙型肝炎患者中AKR1B10的上调与血清甲胎蛋白水平相关，且是肝细胞癌发生的独立危险因素。