Identification of consensus biomarkers for predicting non-genotoxic hepatocarcinogens

Sci Rep. 2017 Jan 24:7:41176. doi: 10.1038/srep41176.

Abstract

The assessment of non-genotoxic hepatocarcinogens (NGHCs) is currently relying on two-year rodent bioassays. Toxicogenomics biomarkers provide a potential alternative method for the prioritization of NGHCs that could be useful for risk assessment. However, previous studies using inconsistently classified chemicals as the training set and a single microarray dataset concluded no consensus biomarkers. In this study, 4 consensus biomarkers of A2m, Ca3, Cxcl1, and Cyp8b1 were identified from four large-scale microarray datasets of the one-day single maximum tolerated dose and a large set of chemicals without inconsistent classifications. Machine learning techniques were subsequently applied to develop prediction models for NGHCs. The final bagging decision tree models were constructed with an average AUC performance of 0.803 for an independent test. A set of 16 chemicals with controversial classifications were reclassified according to the consensus biomarkers. The developed prediction models and identified consensus biomarkers are expected to be potential alternative methods for prioritization of NGHCs for further experimental validation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Carbonic Anhydrase III / genetics
  • Carcinogens / toxicity*
  • Chemokine CXCL1 / genetics
  • Databases, Factual
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / genetics*
  • Machine Learning
  • ROC Curve
  • Risk Assessment
  • Steroid 12-alpha-Hydroxylase / genetics
  • Toxicogenetics / methods*
  • alpha-Macroglobulins / genetics

Substances

  • A2M protein, human
  • Biomarkers, Tumor
  • CXCL1 protein, human
  • Carcinogens
  • Chemokine CXCL1
  • alpha-Macroglobulins
  • Steroid 12-alpha-Hydroxylase
  • Carbonic Anhydrase III