基于生物信息学分析鉴定FMOD作为糖尿病肾病免疫浸润相关标志物OA

Objective:To screen immune infiltration-related genes in diabetic kidney disease(DKD)based on bioinformatics and validate fibromodulin(FMOD)as a potential immune biomarker for DKD.Methods:The kidney sample datasets pertaining to diabetic nephropathy were sourced from the gene expression omnibus(GEO).Specifically,the datasets included GSE111154,which comprises samples from four healthy controls and four individuals with DKD,as well as GSE142025,which consists of samples from nine healthy controls and twenty-eight DKD patients.The Limma R package was employed to identify differentially expressed genes(DEGs),followed by gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)and gene set enrichment analyses(GSEA)to explore the biological functions of these DEGs.Various machine learning algorithms and regression models were applied to identify candidate genes,and the CIBERSORT algorithm was utilized to assess immune cell infiltration and its correlation with the identified candidate genes.Results:A total of 49 DEGs were identified across the GSE111154 and GSE142025 datasets.The DEGs were significantly enriched in cytokine-cytokine receptor interactions,chemokine signaling pathways,and immune-related pathways.Utilizing machine learning algorithms and regression model assessments,FMOD has been recognized as a potential biomarker.CIBERSORT analysis indicated that the expression of FMOD exhibited a significant positive correlation with memory B cells(r=0.73,P<0.05),naïve T cells(r=0.69,P<0.05),regulatory T cells(r=0.58,P<0.05),M2 macrophages(r=0.81,P<0.05),both resting(r=0.73,P<0.05)and activated mast cells(r=0.61,P<0.05),as well as eosinophils(r=0.57,P<0.05).Conversely,FMOD expression demonstrated a negative correlation with resting dendritic cells(r=-0.69,P<0.05).The immune infiltration pattern was highly consistent with the characteristics of the DKD group.Further examination indicated that FMOD was markedly upregulated in DKD and exhibited a negative correlation with estimated glomerular filtration rate(r=-0.75,P<0.01).Conclusion:FMOD may be involved in the occurrence and progression of DKD by regulating immune infiltration.