Validation of Biomarkers and Immunotherapy With Crohn's Disease Using WGCNA and Two-Sample Mendelian Randomization...

Area of Science:

• Biotechnology
• Genomics
• Immunology

Background:

• Crohn's disease (CD) is a chronic inflammatory condition with complex etiology.
• Extraintestinal manifestations and immune dysregulation are common in CD.
• Delayed diagnosis and complications arise from unclear early symptoms and limited detection methods.

Purpose of the Study:

• To identify key genes associated with Crohn's disease (CD).
• To explore the functional roles of identified genes in CD pathogenesis.
• To assess the potential of identified genes as biomarkers for early CD detection.

Main Methods:

• Differentially Expressed Genes (DEG) and Weighted Gene Co-expression Network Analysis (WGCNA) were used to identify key genes.
• Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for functional enrichment.
• Mendelian Randomization (MR) analysis was employed to investigate causal relationships.

Main Results:

• WGCNA identified 3240 differentially expressed genes, highlighting a significant 'magenta' module.
• Enrichment analysis revealed hub genes associated with heme binding, IL-17 signaling, and amoebiasis.
• Top five hub genes identified: CXCL1, LCN2, NOS2, S100A8, and DUOX2, with CXCL1 showing a significant correlation with CD via MR.

Conclusions:

• Five potential biomarker genes (CXCL1, LCN2, NOS2, S100A8, DUOX2) for CD were identified using bioinformatics and MR.
• These genes offer insights into CD pathogenesis and potential therapeutic targets.
• CXCL1 emerged as a promising biomarker for CD with potential for clinical translation.