Identification of Specific Biomarkers and Pathways in the Treatment Response of Infliximab for Inflammatory Bowel Disease: In-Silico Analysis

Abstract

Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. In biological therapy, infliximab became the first anti-tumor necrosis factor (TNF) agent approved for IBD. Despite this success, infliximab is expensive, often ineffective, and associated with adverse events. Prediction of infliximab resistance would improve overall potential outcomes. Therefore, there is a pressing need to widen the scope of investigating the role of genetics in IBD to their association with therapy response. Methods: In the current study, an in-silico analysis of publicly available IBD patient transcriptomics datasets from Gene Expression Omnibus (GEO) are used to identify subsets of differentially expressed genes (DEGs) involved in the pathogenesis of IBD and may serve as potential biomarkers for Infliximab response. Five datasets were found that met the inclusion criteria. The DEGs for datasets were identified using limma R packages through the GEOR2 tool. The probes’ annotated genes in each dataset intersected with DGEs from all other datasets. Enriched gene Ontology Clustering for the identified genes was performed using Metascape to explore the possible connections or interactions between the genes. Results: 174 DEGs between IBD and healthy controls were found from analyzing two datasets (GSE14580 and GSE73661), indicating a possible role in the pathogenesis of IBD. Of the 174 DEGs, five genes (SELE, TREM1, AQP9, FPR2, and HCAR3) were shared between all five datasets. Moreover, these five genes were identified as downregulated in the infliximab responder group compared to the non-responder group. Conclusions: We hypothesize that alteration in the expression of these genes leads to an impaired response to infliximab in IBD patients. Thus, these genes can serve as potential biomarkers for the early detection of compromised infliximab response in IBD patients.

Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach

“…The exact mechanism of AQP9 in IBD remains unclear, but its increased expression in IBD has been observed in previous studies ( 46 , 47 ). Recent research revealed that AQP9 is downregulated in IBD patients’ responders to infliximab compared to non-responders ( 48 ).…”

Exploring Microbial Metabolite Receptors in Inflammatory Bowel Disease: An In Silico Analysis of Their Potential Role in Inflammation and Fibrosis

“…The activation of HCAR2 by butyrate has been demonstrated to protect against experimental colitis through suppressing the inflammatory response in immune cells and reinforcing the intestinal epithelial barrier [ 19 ]. Additionally, HCAR3 overexpression has been found to be decreased in response to a successful anti-TNF-α treatment [ 14 , 15 ], and its activation in innate immune cells has been reported to stimulate their migration [ 20 ], and downregulate the expression of proinflammatory cytokines [ 21 ], thus suggesting a possible protective/anti-inflammatory role of this receptor. However, the exact role of HACR3 in IBD pathophysiology is still unexplored.…”

A Systematic review of Inflammatory biomarkers, Clinical significance, Detection, and their therapeutic agents

“…Quantified inflammatory biomarkers are effective clinical strategy for correct and reasonable drug treatment. Detection inflammatory biomarkers can also be done by using novel methods like proteomic profiling [101] and analysis [102] Commercial tapes (Sebutapes) coated for measuring IL-1α, IL-6, IL-8, INF-γ, TNF-α, and IL-1 [103], CRP was detected by using a Novel Nanoplasmonic Immunoturbidimetry Assay (NanoPITA) [104] and other methods Multiplexing Biosensor [105], Multiplexed protein analysis [106], Multiomics Analysis [107], In-Silico Analysis [108].…”