Detection of Serum Protein Biomarkers for the Diagnosis and Staging of Hepatoblastoma

Int J Mol Sci. 2015 Jun 4;16(6):12669-85. doi: 10.3390/ijms160612669.

Abstract

The present study aimed to identify serum biomarkers for the detection of hepatoblastoma (HB). Serum samples were collected from 71 HB patients (stage I, n = 19; stage II, n = 19, stage III, n = 19; and stage IV, n = 14) and 23 age- and sex-matched healthy children. Differential expression of serum protein markers were screened using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), and the target proteins were isolated and purified using HPLC and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), SEQUEST, and bioinformatics analysis. Differential protein expression was confirmed by enzyme-linked immunosorbent analysis (ELISA). SELDI-TOF-MS screening identified a differentially expressed protein with an m/z of 9348 Da, which was subsequently identified as Apo A-I; its expression was significantly lower in the HB group as compared to the normal control group (1546.67 ± 757.81 vs. 3359.21 ± 999.36, respectively; p < 0.01). Although the expression level decreased with increasing disease stage, pair-wise comparison revealed significant differences in Apo A-I expression between the normal group and the HB subgroups (p < 0.01). ELISA verified the reduced expression of Apo A-I in the HB group. Taken together, these results suggest that Apo A-I may represent a serum protein biomarker of HB. Further studies will assess the value of using Apo A-I expression for HB diagnosis and staging.

Keywords: 2D-LC-LTQ-MS; MALDI-TOF-MS; SELDI-TOF-MS; apolipoprotein A–I; hepatoblastom; protein biomarker.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood*
  • Blood Proteins / analysis*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hepatoblastoma / blood
  • Hepatoblastoma / diagnosis*
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis*
  • Male
  • Neoplasm Staging
  • Prognosis
  • Protein Array Analysis
  • Proteomics / methods*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Biomarkers, Tumor
  • Blood Proteins