Blood transcriptomics identifies FEZ1 as a novel non-invasive diagnostic biomarker for inflammatory bowel disease

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Abstract

In comparison with conventional diagnostic methods, blood biomarkers are an easily accessible source for diagnosing inflammatory bowel disease (IBD). To identify such a biomarker, an integrated transcriptomics approach was employed to detect RNAs exhibiting diagnostic efficacy. For this purpose, four gene expression datasets obtained from blood specimens were integrated (GSE119600, GSE94648, GSE86434, and GSE71730). After determining differentially expressed genes in Crohn’s disease and ulcerative colitis, DEGs in IBD were defined as genes with a consistent direction of alteration in both disorders. Mapping the PPI network for these genes revealed TNF as the central hub gene. Subsequently, weighted gene-expression network analysis (WGCNA) was carried out to determine IBD-specific modules. Considering the degree metrics, module membership, and gene significance, PRF1 was the only gene discerned as a hub gene in a module that was prominently enriched in IBD. Genes with converging results from differential expression analysis and WGCNA were subjected to the random forest decision tree-based and LASSO regression methods. Following the identification of FEZ1 and NLRC5 as genes highlighted by both analyses, ROC analysis was applied to assess their diagnostic potential. Although both genes demonstrated acceptable diagnostic efficacy in the integrated data, only FEZ1 was considered as a potential biomarker based on the replication of results in validation datasets (GSE119600, GSE94648, GSE86434, and GSE71730). While autophagy is currently the most convincing explanation for the involvement of FEZ1 in IBD, further investigations are required to elucidate its immunological role.

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