(WHS-L4.02) DNA Methylation Profiling for the Prediction of Recurrences and Prognosis in Patients with Diabetic Foot Ulcers
Thursday, May 16, 2024
10:30 AM – 11:30 AM East Coast USA Time
Background: Diabetic foot ulcers (DFUs) are recalcitrant to healing. However, the molecular mechanism causing this dysfunction is not fully understood. DNA methylation profiles change during the proliferation, differentiation, and development of an organism, resulting in tissue or disease identification. To elucidate the biomarkers for DFU prognosis, we hypothesized that differences in DNA methylation patterns could provide important therapeutic targets in the treatment of DFUs.
Methods: We collected 48 blood samples from 36 DFU patients treated at Korea University Guro Hospital from October 2019 to November 2021. The Illumina MethylationEPIC (850k) DNA methylation microarray was used to determine the pattern between differentially methylated regions (DMRs) in DFU patients with good or poor prognoses. We then selected and visualized the DMRs in the form of heatmaps, and enriched terms associated with these DMRs were identified. By using the DMR list in two processes, Kyoto Gene and Genome Encyclopedia (KEGG) and gene ontology (GO) analysis, gene-concept network, GSEA, and decision tree were performed.
Results: In total, 92 DMRs and 108 DMRs (|Log2 fold change| > 0.1 and P < 0.03) were hypermethylated and hypomethylated, respectively. In the good prognosis sample, 69 and 156 DMRs were hypermethylated and hypomethylated, respectively. In the KEGG analysis, the MAPK signaling pathway was commonly detected as the highest pathway. In the decision tree, MORN1 hypomethylation and NCOR2 hypermethylation were crucial classifiers by recurrence.
Conclusion: Collectively, MORN1 and NCOR2 genes may be used as biomarkers for predicting the recurrences and prognosis in DFU patients. In DFUs, the clues of recurrence and prognosis prediction may be provided through DMRs and the molecular mechanisms related to inflammation.