Transcriptomics-driven drug repositioning for the treatment of diabetic foot ulcer

Abstract

Diabetic foot ulcers (DFUs) are a common complication of diabetes and can lead to severe disability and even amputation. Despite advances in treatment, there is currently no cure for DFUs and available drugs for treatment are limited. This study aimed to identify new candidate drugs and repurpose existing drugs to treat DFUs based on transcriptomics analysis. A total of 31 differentially expressed genes (DEGs) were identified and used to prioritize the biological risk genes for DFUs. Further investigation using the database DGIdb revealed 12 druggable target genes among 50 biological DFU risk genes, corresponding to 31 drugs. Interestingly, we highlighted that two drugs (urokinase and lidocaine) are under clinical investigation for DFU and 29 drugs are potential candidates to be repurposed for DFU therapy. The top 5 potential biomarkers for DFU from our findings are IL6ST, CXCL9, IL1R1, CXCR2, and IL10. This study highlights IL1R1 as a highly promising biomarker for DFU due to its high systemic score in functional annotations, that can be targeted with an existing drug, Anakinra. Our study proposed that the integration of transcriptomic and bioinformatic-based approaches has the potential to drive drug repurposing for DFUs. Further research will further examine the mechanisms by which targeting IL1R1 can be used to treat DFU.

Integrated genomic network analysis revealed potential of a druggable target for hemorrhoid treatment

“…We meticulously executed a rigorous functional annotation process to identify genes associated with the biological risk of hemorrhoids. To prioritize genes for potential drug discovery within the confines of this study, we adopted a scoring system previously employed and documented in various research publications ( Irham et al, 2020 , Adikusuma et al, 2021 , Adikusuma et al, 2022 , Afief et al, 2022 , Zazuli et al, 2022 , Adikusuma et al, 2023 ). The ensuing description presents the outcomes of the scoring process across five functional annotations: 1) genes prioritized via KOMP (n = 22); 2) genes prioritized through KEGG (n = 22); 3) genes prioritized based on BP (n = 67); 4) genes prioritized based on CC (n = 24); and 5) genes prioritized based on MF (n = 33).…”

A novel diabetic foot ulcer diagnostic model: identification and analysis of genes related to glutamine metabolism and immune infiltration

“…Research on biomarkers in the context of DFU is still relatively limited. Recently, bioinformatics analysis has become a valuable tool for exploring the intricate and complex connections between cell apoptosis and DFU [ 56 , 57 ]. A comprehensive study has indicated and identified potential biomarkers associated with DFU through transcriptomics and proteomics bioinformatic models, and a study has shown that CXCL11, DDX60, IFI44, and IFI44L are key hub genes with the potential to serve as molecular targets for immunotherapy in DFU [ 58 ].…”