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Published on: June 9, 2021
Bioinformatics-based analysis and experimental validation of PANoptosis-related biomarkers and immune infiltration in
Su Zhang1,2, Yun Zhang3, Weitao Hu4
1The Second Clinical College of Fujian Medical University, Quanzhou, China.
Background:
Diabetic nephropathy (DN) is a frequent and serious microvascular complication of diabetes. PANoptosis is a novel mode of cell death that encompasses apoptosis, necrosis and pyroptosis. However, effective PANoptosis-related biomarkers for DN are currently lacking. Therefore, this study aimed to elucidate the role of PANoptosis-related genes (PRGs) in the development of DN and their potential as diagnostic markers of DN, as well as their association with immune cell infiltration.
Materials And Methods:
We retrieved the DN-related dataset GSE30122 from the GEO database. Then differentially expressed genes (DEGs) were identified and DEGs were analyzed for functional enrichment. In addition, we obtained key gene modules by WGCNA. Subsequently, we gained the intersecting genes of DEGs, key gene modules and PRGs. Four algorithms were further used to screen the key DE-PRGs in DN (DNDE-PRGs). We also investigated the biological functions of the key DNDE-PRGs by GSEA software. Furthermore, we analyzed the immune infiltration of DN tissues. The correlation of key genes with glomerular filtration rate (GFR) and blood urea nitrogen (BUN) was also examined. Finally, key genes were validated using clinical samples and db/db mice.
Results:
We identified two key DNDE-PRGs (AKT3 and FYN). They showed good diagnostic value in the DN. And they were associated with immune cell infiltration. In addition, they have a correlation with GFR and BUN. Finally, they were validated in clinical samples and animal experiments.
Conclusion:
AKT3 and FYN may be good PANoptosis-related biomarkers in DN. This provides new insights into the pathogenesis of DN.
Insights
Researchers identified AKT3 and FYN as key PANoptosis-related genes (PRGs) in diabetic nephropathy (DN). These genes show diagnostic potential and link to immune infiltration and kidney function markers, offering new insights into DN pathogenesis.
Area of Science:
- Nephrology
- Genetics
- Cell Biology
Background:
- Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by microvascular damage.
- PANoptosis, a novel cell death pathway, is implicated in disease, but its role and biomarkers in DN remain unclear.
- Current diagnostic tools for DN lack effective PANoptosis-related markers.
Purpose of the Study:
- To investigate the role of PANoptosis-related genes (PRGs) in DN development.
- To identify potential diagnostic biomarkers for DN among PRGs.
- To explore the association of PRGs with immune cell infiltration and kidney function in DN.
Main Methods:
- Utilized the GEO dataset GSE30122 for DN analysis.
- Applied differential gene expression (DEG) analysis and Weighted Gene Co-expression Network Analysis (WGCNA).
- Screened key differentially expressed PRGs (DNDE-PRGs) using four algorithms and validated findings in clinical samples and db/db mice.
Main Results:
- Identified AKT3 and FYN as two key DNDE-PRGs in DN.
- These genes demonstrated significant diagnostic value for DN.
- AKT3 and FYN correlated with immune cell infiltration, glomerular filtration rate (GFR), and blood urea nitrogen (BUN).
Conclusions:
- AKT3 and FYN emerge as promising PANoptosis-related biomarkers for diabetic nephropathy.
- These findings offer novel perspectives into the underlying mechanisms of DN.
- Further research into AKT3 and FYN could lead to improved diagnostic strategies for DN.

