From polyamine metabolism genes to immunoproteasome subunits: a transcriptome-based screening of candidate biomarkers in Crohn's disease.

This study explored Polyamine metabolism (PM)-related biomarkers and their regulatory processes in Crohn's disease (CD) using three transcriptome datasets (GSE179285, GSE126124, and GSE102133) and 59 PM-related genes (PMRGs). Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were employed to identify candidate genes, resulting in four key candidates: PSMB10, PSMB8, PSMB9, and PSME2, selected from 796 differentially expressed genes (DEGs). Machine learning and expression validation confirmed that PSMB9, PSMB10, and PSME2 were overexpressed in the CD group, with ROC curve analysis revealing AUC values above 0.8 in all three datasets, supporting their potential as biomarkers. Functional enrichment analysis showed their involvement in the degradation of valine, leucine, and isoleucine, and cell adhesion molecules. Immune infiltration analysis, inferred from the same transcriptomic data, showed that the expression levels of these genes were positively correlated with the abundance of 27 immune cell types in CD tissues. Additionally, these biomarkers were linked to other digestive diseases, such as colon disease and proctitis. Notably, CARFILZOMIB demonstrated significant binding to these biomarkers, suggesting a potential mechanistic link that warrants further experimental investigation. This research emphasizes the role of PSMB9, PSMB10, and PSME2 as promising biomarkers for CD and provides a foundation for further exploration of the regulatory mechanisms of PM in CD.