ArticleFASEB bioAdvances2026
HIF1A-Associated Ferroptosis-Related Gene Signatures Reveal Candidate Circulating Biomarkers in Diabetic Nephropathy.
Article in FASEB bioAdvances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Diabetic nephropathy (DN) is a major microvascular complication of diabetes. Hypoxia-inducible factor 1-alpha (HIF1A) and ferroptosis contribute to the progression of DN, but the circulating biomarkers associated with these pathways are still unknown. In this study, the whole-blood transcriptomic datasets in the Gene Expression Omnibus were combined with ferroptosis-related genes from the FerrDb database and published literature. The differentially expressed genes of HIF1A and of DN were intersected, and then the feature selection with Boruta and SVM-RFE was performed, followed by external validation, immune infiltration analysis, prediction of regulatory network, drug-target prediction, and RT-qPCR validation. We identified 773 HIF1A-related genes, 1445 DN-related genes, and 22 overlapping candidate genes. Using machine-learning analysis, nine core genes were identified, including SLC7A5 and SLC2A14, which consistently upregulated in both training and validation datasets and corroborated by RT-qPCR. Both genes were positively associated with activated natural killer cells and negatively associated with monocytes in estimated circulating immune-cell composition analysis. Regulatory-network and DrugBank analyses generated hypotheses regarding upstream miRNAs and potential compound interaction. These findings identify SLC7A5 and SLC2A14 as candidate circulating biomarkers related to HIF1A expression and ferroptosis-related gene signatures in DN. Further large-cohort and functional studies are required to confirm their diagnostic and mechanistic relevance.
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