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

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.

Omics data integration identifies ELOVL7 and MMD gene regions as novel loci for adalimumab response in patients with Crohn’s disease

“…Anti-TNF therapy is of pivotal importance in patients with CD and genomic biomarkers that would tailor personalized treatment are currently needed, in particular as new biologicals for CD treatment have recently emerged. In the recent systematic review of anti-TNF genomic biomarkers in CD, it was noted that almost no candidate gene could be confirmed in an independent association study and no overlap was detected among genes identified with association and gene expression studies 18 . In the present study, we have adopted a new approach 19 for the integration of PBMCs derived transcriptomic and genomic data.…”

“…Several studies have focused on genetic background and gene expression 11 – 17 as potential biomarkers for anti-TNF treatment response. Currently the genomics markers of anti-TNF response in CD are not reaching significant thresholds and practically no reproducibility between genetic and expression markers exists, as identified by the first integration of genomic and expression data prior to anti-TNF treatment in a systematic review 18 . Prediction profiles have been mostly identified using epithelial gene expression data for which colonoscopy and biopsy sampling are needed 16 , 17 .…”

“…We also included four genes that correlated with changes in endoscopic activity in UC patients with anti-TNF therapy and three differentially expressed genes between responding and non-responding IBD patients to anti-TNF therapy as identified by a cell-centered meta-analysis (Table 1 ) 21 , 22 . Additionally we included 12 independently confirmed and previously integrated genomic and expression (RNA and protein) markers of anti-TNF therapy response in CD patients (Table 1 ) 18 . The investigation gene panel built for the present study was altogether based on 65 previously suggested candidate genes in 2126 individuals with IBD and 34 individuals with RA, and treated with anti-TNF therapy.…”

A systematic review and meta-analysis: Female smokers,even former smokers lead higher incidence of psoriasis in the treatment of inflammatory bowel disease with biological agents.

“…Many clinical manifestations can be used to predict side effects may be inadvertently ignored by physicians. The genetic expressiom markers were studied for prediction of TNF antagonists induced psoriasis [53]. Some studies suggested that suspending the use of biological agents or extending the duration of drug therapy has no effect on the relief of drug-induced psoriasis [54][55][56].…”

Assessment of Dysregulation of HERC6 and Essential Biological Processes in Response to Laser Therapy of Human Arm Skin

“…This approach identifies molecular functions, cellular components, biological processes, and biochemical pathways related to the studied genes. 10 Physical and chemical properties of genes and their regulatory effects on each other provide useful information to screen and rank a set of genes to find the crucial ones. Activation, inhibition, catalysis, binding, reaction, and post-translation modification actions can be determined when an action map is plotted.…”