Lumican Identified as Key Extracellular Matrix-Related Biomarker in Diabetic Nephropathy Through Integrated Bioinformatics Analysis

This study highlights lumican as a promising biomarker for predicting the onset and progression of diabetic nephropathy and reveals its close association with extracellular matrix remodeling, a hallmark of diabetic kidney disease. The findings offer new perspectives for the clinical diagnosis and targeted treatment of diabetic nephropathy, potentially improving patient outcomes.

Using computational bioinformatics techniques, potential biomarkers for diabetic nephropathy were identified, with a particular emphasis on the key gene lumican and its involvement in disease-related molecular mechanisms. Publicly accessible microarray datasets, GSE96804 and GSE30528, from the Gene Expression Omnibus database were analyzed to detect genes that were differentially expressed between diabetic nephropathy patients and healthy controls. Gene Ontology enrichment analysis and Gene Set Enrichment Analysis based on the Kyoto Encyclopedia of Genes and Genomes database revealed that these differentially expressed genes were significantly involved in biological processes such as the cellular response to hexose and organization of cell–cell junctions, as well as pathways related to amino acid metabolism and adipokine signaling. Central regulatory genes were identified using Cytoscape software, and their clinical significance was further explored using the Nephroseq database. These genes were found to be upregulated in kidney tissues of patients with diabetic nephropathy, and their expression levels showed a negative correlation with estimated glomerular filtration rate, indicating deterioration in renal function. Among the core genes, lumican demonstrated substantial overexpression in diabetic nephropathy tissues, which was validated through immunohistochemistry and immunofluorescence using patient samples. Functional enrichment analysis of lumican and its interacting protein network revealed their strong association with extracellular matrix organization. These results establish lumican as a potential diagnostic and therapeutic target in diabetic nephropathy and provide novel insights into the underlying mechanisms of kidney tissue remodeling in the context of diabetes.