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

Int J Radiat Biol. 2018 Apr;94(4):315-326. doi: 10.1080/09553002.2018.1439193. Epub 2018 Mar 2.

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.

Keywords: Low-dose-rate γ-irradiation; biomarkers; hepatocellular adenoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / blood
  • Adenoma / diagnosis*
  • Adenoma / etiology
  • Animals
  • Biomarkers, Tumor / blood*
  • Female
  • Gamma Rays
  • Glycoproteins / blood*
  • Immunoglobulins / blood*
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / etiology
  • Mice
  • Neoplasms, Radiation-Induced / blood
  • Neoplasms, Radiation-Induced / diagnosis*
  • Prostatic Secretory Proteins / blood
  • Radiation Dosage
  • Transcriptome
  • Trypsin Inhibitor, Kazal Pancreatic / blood
  • alpha-Fetoproteins / analysis

Substances

  • A1bg protein, mouse
  • Biomarkers, Tumor
  • Glycoproteins
  • Immunoglobulins
  • Prostatic Secretory Proteins
  • Spink1 protein, mouse
  • alpha-Fetoproteins
  • Trypsin Inhibitor, Kazal Pancreatic