ArticleBiomedicines2023
Identifying Aging-Related Biomarkers and Immune Infiltration Features in Diabetic Nephropathy Using Integrative Bioinformatics Approaches and Machine-Learning Strategies.
Article in Biomedicines, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Senescent BMSC-Derived Thbs1 Drives Inflammaging and Impairs Bone Regeneration by Suppressing PINK1/Parkin-Mediated Mitophagy in Macrophages.Aging cell · 2026Article
- Molecular crosstalk between AHR, CYP1B1, and ITGAM in diabetic nephropathy: Integrated insights from bioinformatics and experimental validation.Biochemistry and biophysics reports · 2026Article
- Progression of early diagnostic markers for diabetic kidney disease: From single-indicator detection to multi-omics integration modeling.Current research in physiology · 2026Review
- Screening Autophagy-Related DKD Biomarkers Based on Bulk RNA and Single-Cell Analysis and Uncovering Their Regulatory Mechanisms in DKD Renal Fibrosis.Journal of diabetes research · 2026Article
- CD93: A Promising NETs-Related Biomarker for Diagnosis and Therapy in Actinic Keratosis.OncoTargets and therapy · 2025Article
- Exploring the potential mechanisms of Tongmai Jiangtang capsules in treating diabetic nephropathy through multi-dimensional data.Frontiers in endocrinology · 2023Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAging plays an essential role in the development of diabetic nephropathy (DN). This study aimed to identify and verify potential aging-related genes associated with DN using bioinformatics analysis.
methodsTo begin with, we combined the datasets from GEO microarrays (GSE104954 and GSE30528) to find the genes that were differentially expressed (DEGs) across samples from DN and healthy patient populations. By overlapping DEGs, weighted co-expression network analysis (WGCNA), and 1357 aging-related genes (ARGs), differentially expressed ARGs (DEARGs) were discovered. We next performed functional analysis to determine DEARGs' possible roles. Moreover, protein-protein interactions were examined using STRING. The hub DEARGs were identified using the CytoHubba, MCODE, and LASSO algorithms. We next used two validation datasets and Receiver Operating Characteristic (ROC) curves to determine the diagnostic significance of the hub DEARGs. RT-qPCR, meanwhile, was used to confirm the hub DEARGs' expression levels in vitro. In addition, we investigated the relationships between immune cells and hub DEARGs. Next, Gene Set Enrichment Analysis (GSEA) was used to identify each biomarker's biological role. The hub DEARGs' subcellular location and cell subpopulations were both identified and predicted using the HPA and COMPARTMENTS databases, respectively. Finally, drug-protein interactions were predicted and validated using STITCH and AutoDock Vina.
resultsA total of 57 DEARGs were identified, and functional analysis reveals that they play a major role in inflammatory processes and immunomodulation in DN. In particular, aging and the AGE-RAGE signaling pathway in diabetic complications are significantly enriched. Four hub DEARGs (CCR2, VCAM1, CSF1R, and ITGAM) were further screened using the interaction network, CytoHubba, MCODE, and LASSO algorithms. The results above were further supported by validation sets, ROC curves, and RT-qPCR. According to an evaluation of immune infiltration, DN had significantly more resting mast cells and delta gamma T cells but fewer regulatory T cells and active mast cells. Four DEARGs have statistical correlations with them as well. Further investigation revealed that four DEARGs were implicated in immune cell abnormalities and regulated a wide range of immunological and inflammatory responses. Furthermore, the drug-protein interactions included four possible therapeutic medicines that target four DEARGs, and molecular docking could make this association practical.
conclusionsThis study identified four DEARGs (CCR2, VCAM1, CSF1R, and ITGAM) associated with DN, which might play a key role in the development of DN and could be potential biomarkers in DN.
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