The following is a summary of “Bioinformatics Exploration of Immune Cell Infiltration Patterns and Diagnostic Biomarkers in Atherosclerosis,” published in the November 2023 issue of Gastroenterology by Ji et al.
This research aims to explore practical diagnostic markers and unravel the molecular underpinnings of atherosclerosis, focusing on immune cell infiltration through bioinformatics analysis. Researchers accessed expression profile datasets (GSE28829 and GSE43292) from the GEO database, comprising individuals with atherosclerosis and healthy controls. The Molecular Signatures Database was utilized to gather genes linked to glutamine metabolism.
Employing the limma package in R, they identified 308 differentially expressed genes and GLN-associated genes. Weighted Gene Co-expression Network Analysis aided in filtering significant modules. Gene Set Enrichment Analysis and Gene Set Variation Analysis were conducted on MSigDB sets. The biological functions of DEGs were scrutinized using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
The investigators used STRING and Cytoscape software to delineate hub genes and functional modules through protein-protein interaction (PPI) network analysis. xCell software enabled the assessment of immune and stromal cell composition patterns. Correlation analyses were performed between key genes and immune cell subtypes.
Functional enrichment analysis revealed strong enrichment in biological processes such as muscle contractility, muscle tissue development, cuticle fiber, mycobacterial binding, and actin binding. Enriched KEGG pathways encompassed dilated cardiomyopathy, hypertrophic cardiomyopathy, and the cAMP signaling pathway. Among the identified hub genes, 27 showed high diagnostic potential, as indicated by the relatively high area under the curve values.
Furthermore, the analysis demonstrated significantly higher infiltration levels of immune cells in the atherosclerosis group compared to the control group. This study underscores 27 GLN-associated genes as potential diagnostic biomarkers for atherosclerosis, offering new insights into immune responses and facilitating a deeper understanding of the molecular mechanisms underlying this condition.