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Original Articles

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

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Pages 315-326 | Received 21 Jul 2017, Accepted 01 Feb 2018, Published online: 02 Mar 2018
 

Abstract

Purpose: Chronic low-dose-rate (20 mGy/day) γ-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 γ-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 4181 genes differentially expressed in HCAs (>2.0-fold). From these genes, those for α-fetoprotein (Afp), α-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.

Acknowledgements

This work was performed under contract with the Aomori Prefectural Government, Japan. We also thank Mr. K. Ichinohe (IES) and Mr. M. Yoneya (IES) for providing technical assistance in bleeding mice. The microarray data presented in this paper have been deposited in Gene Expression Omnibus (GEO).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Aomori Prefectural Government. Aomori Prefectural Government does not provide a grant number.

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