Screening of biomarkers for liver adenoma in low-dose-rate gamma-ray-irradiated mice.

Purpose: Chronic low-dose-rate (20 mGy/d) gamma-irradiation increases the incidence of hepatocellular adenomas (HCA) in female B6C3F1 mice. The purpose of this study is to identify potential serum biomarkers for these HCAs by a new approach. Material and methods: Microarray analysis were performed to compare the gene expression profiles of HCAs from mice exposed to low-dose-rate gamma rays with those of normal livers from non-irradiated mice. From the differentially expressed genes, those for possibly secretory proteins were selected. Then the levels of the proteins in sera were analysed by ELISA. Results: Microarray analysis identified 4,181 genes differentially expressed in HCAs (>2.0-fold). From these genes, those for Alpha-fetoprotein (Afp), Alpha-1B- glycoprotein (A1bg) and Serine peptidase inhibitor Kazal type 3 (Spink3) were selected as the genes for candidate proteins. ELISA revealed that the levels of Afp and A1bg proteins in sera significantly increased and decreased, respectively, in low dose-rate irradiated mice with HCAs and also same tendency was observed in human patients with hepatocellular carcinomas. Conclusion: These results indicate that A1bg could be a new serum biomarker for liver tumor. This new approach of using microarray to select genes for secretory proteins is useful for prediction of novel tumor markers in sera.