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Published on: March 15, 2024
Ferroptosis-related differentially expressed genes in patients with diabetes
Zhiyuan Li1, Jianjun Yan2, Ruiying Zhang2
1Department of Heart Center, The Third Central Hospital of Tianjin, Jintang Road 83, Hedong District, Tianjin, 300070 China.
Background:
Type 2 diabetes mellitus (DM) can lead to multiple organs damage, for instance, lower limbs, kidneys, nerves and heart. We aimed to investigate the differentially expressed genes (DEGs) that might be potential targets for DM patients, which may promote multiple organs damage.
Methods:
GSE95849 and GSE25724 were downloaded and analyzed to obtain DEGs. A Venn diagram was used to obtain the overlapping ferroptosis-related DEGs using the Ferroptosis Database. Enrichment pathway analysis was performed and the hub genes were obtained. Pivotal miRNAs, transcription factors and drugs with the hub genes interactions were also predicted. Human blood samples were utilized to investigate the effects of the hub genes on DM progression.
Results:
Utilizing the Limma package, 3796 up-regulated and 2475 down-regulated DEGs were obtained in GSE25724, while 5101 up-regulated and 842 down-regulated DEGs were obtained in GSE95849. Using Venn diagram, 28 ferroptosis-related DEGs were obtained. The list of ferroptosis-related DEGs was analyzed, which were involved in response to oxidative stress, cellular response to external stimulus, secondary lysosome, autophagosome, Prolactin signaling pathway, Ferroptosis, and IL-17 signaling pathway. In the protein-protein interaction network, the ferroptosis-related DEGs, including STAT3, SRC, MAPK3, CTBB, ELAVL1, PRKAA1, NFE2L2, PTGS2, MAPK1 and EIF2S1, were demonstrated the hub genes using MCC algorithm in CytoHubba plug-in. TFs interactions, miRNA interactions and drugs interactions with hub genes were explored, which demonstrated the drugs of the targets, for instance, PTGS2, RSG4, MAPK1, MAPK3 and PRKAA1.After validation of human blood samples, STAT3, CTBB, MAPK1 and EIF2S1 were validated to be highly expressed in diabetic patients compared to normal individuals.
Conclusions:
The screened hub genes, STAT3, CTBB, MAPK1 and EIF2S1 were validated to be highly expressed in diabetic patients compared to normal individuals, which may be potential therapeutic targets to treat diabetes and improve patients' prognosis.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s40200-025-01740-3.
Insights
Type 2 diabetes mellitus (DM) can damage multiple organs. This study identified key genes (STAT3, CTBB, MAPK1, EIF2S1) involved in ferroptosis that are highly expressed in diabetic patients, suggesting potential therapeutic targets.
Area of Science:
- Genomics
- Molecular Biology
- Diabetology
Background:
- Type 2 diabetes mellitus (DM) is associated with multi-organ damage.
- Identifying specific molecular targets is crucial for managing DM complications.
Purpose of the Study:
- To investigate differentially expressed genes (DEGs) related to ferroptosis in Type 2 DM.
- To identify potential therapeutic targets for DM patients.
Main Methods:
- Analysis of gene expression datasets (GSE95849, GSE25724) to identify DEGs.
- Utilized Venn diagrams and the Ferroptosis Database to find overlapping ferroptosis-related DEGs.
- Performed pathway enrichment analysis and protein-protein interaction network analysis to identify hub genes.
- Validated hub gene expression in human blood samples from diabetic patients.
Main Results:
- Identified 28 ferroptosis-related DEGs involved in oxidative stress, cellular response, and signaling pathways.
- Key hub genes including STAT3, SRC, MAPK3, CTBB, ELAVL1, PRKAA1, NFE2L2, PTGS2, MAPK1, and EIF2S1 were identified.
- STAT3, CTBB, MAPK1, and EIF2S1 were validated as highly expressed in diabetic patients compared to controls.
Conclusions:
- STAT3, CTBB, MAPK1, and EIF2S1 are potential therapeutic targets for Type 2 DM.
- These genes may play a significant role in DM progression and multi-organ damage.
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