Integrated Bioinformatics Analysis Identifies ELAVL1 and APP as Candidate Crucial Genes for Crohn's Disease.

Heli Li,Shiran Sun,Qianru Li,Xiong Cai,Ping Lei,Guanxin Shen

doi:10.1155/2020/3067273

Abstract

Immune imbalance and barrier destruction of intestinal mucosa are the central pathogenic factors of Crohn's disease (CD). In this study, three independent microarray studies of CD were integrated and 9912 differentially expressed genes (DEGs) were analysed by NetworkAnalyst to screen candidate crucial genes. NetworkAnalyst identified ELAV-like RNA binding protein 1 (ELAVL1) as the most crucial upregulated gene and amyloid-β precursor protein (APP) as the most crucial downregulated gene in peripheral blood of CD patients. By computing significance with hypergeometric test based on the KEGG pathway database, upregulated DEGs highlight the pathways of T cell receptor signaling and the differentiation of T helpers. Downregulated DEGs were found enriched in pathways in multiple cancers, MAPK signaling, Rap1 signaling, and PI3K-AKT signaling. Further taking all DEGs together, Gene Set Enrichment Analysis (GSEA) brought out the NOD-like receptor (NLR) signaling pathway which could be regulated by ELAVL1. xCell found decreased naïve and differentiated T cell proportions in the peripheral blood of CD patients suggesting T cell migration to the intestinal tissue and/or exhaustion. Further, ELAVL1 expression correlating with multiple T cell proportions suggests that ELAVL1 may regulate T cell activation. These findings illustrated that ELAVL1 and APP were candidate crucial genes in the peripheral blood of CD patients. ELAVL1 possibly acts as a key regulator of T cell activation via the NLR signaling pathway. APP might be a downstream effector of infliximab treatment connecting with MAPK signaling.

Highlights

Crohn’s disease (CD), as a systemic inflammatory disease, mainly influences the gastrointestinal tract with a wide range of contributing factors including host genetics, immune system, environmental exposures, and the gut microbiome [1]
To remove this batch effect, parametric empirical Bayes frameworks provided by ComBat function were applied by NetworkAnalyst
Since we have found that ELAV-like RNA binding protein 1 (ELAVL1) is closely associated to NOD-like receptor (NLR) signaling, which has an important impact on priming the activation of T cells, we further investigate the association between ELAVL1 expression and the xCell scores of T cells in CD patients by the Spearman correlation

Summary

Introduction

Crohn’s disease (CD), as a systemic inflammatory disease, mainly influences the gastrointestinal tract with a wide range of contributing factors including host genetics, immune system, environmental exposures, and the gut microbiome [1]. Like dendritic cells, recognize the antigens via pattern recognition receptors, such as Toll-like receptors (TLR) and NLR, and regulate the activation of T cells [3]. Among the factors associated with CD in immune system, T cells were highlighted in CD pathology because about 200 CD risk loci are involved in T cell signaling [4, 5]. The CD4+ T cell, including Th1, Th17, and regulatory T (Treg) cells, were associated with the severity of CD, with active inflammation [2]. CD8+ T cell transcriptional signatures were identified as reliable prognostic biomarkers in the blood of CD patients [6, 7]. One T cell subtype from the blood of CD patients is enriched for the CD-risk gene [9].

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Results

Conclusion