HMOX1 as a Novel Biomarker for Glucose–Lipid Metabolism Disorder and T2DM: Systematic Bioinformatics Investigation and Experimental Verification

Abstract

Type 2 diabetes mellitus (T2DM) has led to a considerable increase in morbidity and mortality worldwide. Current treatments control blood glucose but cannot reverse the disease, making it important to identify biomarkers that predict T2DM onset and progression. This study explores heme oxygenase 1(HMOX1) as a novel biomarker for T2DM through bioinformatics and experimental validation. Core differentially expressed genes (DEGs) were identified using the Gene Expression Omnibus database, with Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis analyses revealing notable pathways, including Toll-like receptor signaling and cytokine receptor interactions. A Nomogram model and receiver operating characteristic curves demonstrated strong diagnostic effectiveness for these core DEGs. The CIBERSORT algorithm assessed the relation between core DEGs and immune cell infiltration, showing substantial associations with several immune cell types, particularly highlighting HMOX1’s correlation with eight immune cells (p < 0.05). In a mouse model, db/db mice displayed typical diabetic characteristics and lower serum HMOX1 levels compared to db/m controls (p < 0.01). Histological analysis confirmed liver damage and decreased expression of NFE2L2 and HMOX1 in diabetic mice tissues (p < 0.05). HMOX1 is identified as a promising biomarker for T2DM, with its downregulation confirmed through bioinformatics and experimental methods.