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

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. 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.