Identification and Confirmation of Shared Etiology and Hub Biomarkers in Nonalcoholic Steatohepatitis and Crohn's Disease.

Purpose: Non-alcoholic steatohepatitis (NASH) and Crohn's disease (CD) are interconnected through shared pathophysiological processes. Our goal was to identify the key molecules and pathways involved in their coexistence.

Methods: We conducted a comprehensive quantitative bioinformatic analysis utilizing publicly accessible RNA sequencing datasets from the Gene Expression Omnibus (GEO) database, specifically the datasets GSE186582 for Crohn's Disease (CD) and GSE164760 for Non-Alcoholic Steatohepatitis (NASH). Differentially expressed genes (DEGs) were identified using the R packages "edgeR" and "limma." Functional characterization of these DEGs was performed through gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Protein-protein interaction networks of the DEGs were constructed using STRING and visualized with Cytoscape, with key hub genes identified via the cytoHubba plugin. To validate these hub genes, we employed independent datasets, GSE20881 for CD and GSE63067 for NASH.

Results: In total, 104 common DEGs were identified, with 62 being downregulated and 42 upregulated. Both CD and NASH showed enhanced amino acid production and metabolism. Notably, ten hub genes-GLUL, COL3A1, CTH, PDGFRA, GOT1, PECAM1, FCER1G, NOTCH2, PC, and ASPA-emerged as central players. ROC analysis pinpointed GLUL as a significant hub gene, displaying an area under the curve of > 0.8 for both CD and NASH; this was further validated by RT-qPCR. Additionally, the transcription factors SRF and YY1, predicted by this hub gene, showed marked differential expression in both NASH and CD.

Conclusion: Collectively, our findings shed light on a potential shared pathogenesis between NASH and CD, with the hub gene GLUL offering promising diagnostic and therapeutic insights.