Pre-Treatment Biomarkers of Anti-Tumour Necrosis Factor Therapy Response in Crohn's Disease-A Systematic Review and Gene Ontology Analysis

Cells. 2019 May 28;8(6):515. doi: 10.3390/cells8060515.

Abstract

The most prominent treatment for the serious cases of Crohn's disease (CD) are biological tumour necrosis factor (TNF) inhibitors. Unfortunately, therapy nonresponse is still a serious issue in ~1/3 of CD patients. Accurate prediction of responsiveness prior to therapy start would therefore be of great value. Clinical predictors have, however, proved insufficient. Here, we integrate genomic and expression data on potential pre-treatment biomarkers of anti-TNF nonresponse. We show that there is almost no overlap between genomic (annotated with tissue-specific expression quantitative trait loci data) and transcription (RNA and protein data) biomarkers. Furthermore, using interaction networks we demonstrate there is little direct interaction between the proposed biomarkers, though a majority do have common interactors connecting them into networks. Our gene ontology analysis shows that these networks have roles in apoptotic signalling, response to oxidative stress and inflammation pathways. We conclude that a more systematic approach with genome-wide search of genomic and expression biomarkers in the same patients is needed in future studies.

Keywords: Crohn’s disease; adalimumab; anti-tumour necrosis factor; biomarker; certolizumab pegol; inflammatory bowel disease; infliximab; therapy response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Biomarkers / blood
  • Biomarkers / metabolism*
  • Crohn Disease / blood
  • Crohn Disease / drug therapy*
  • Crohn Disease / genetics*
  • Gene Ontology*
  • Genome, Human
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • RNA / genetics
  • RNA / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Biomarkers
  • Tumor Necrosis Factor-alpha
  • RNA