A diabetic foot consortium study: Evaluation of tissue biomarkers for predicting DFU healing

Summary: Abstract Body: Diabetic foot ulcers (DFUs) are a major clinical problem characterized by high morbidity, disability, amputations and mortality. A key challenge to the early use of advanced therapies for DFUs is lack of predictive biomarkers to guide therapeutic decisions. Thus, we conducted the first multicenter observational study of the recently established NIDDK Diabetic Foot Consortium (DFC) to test if either of the two previously identified tissue biomarkers, c-myc and phosphorylated-glucocorticoid receptor (p-GR), could predict complete healing after week 12 follow-up in 107 participants. Originally aiming for 213 participants, the study was stopped early due to slow enrollment and lack of biomarker significance in interim analyses. Wound edge tissue was collected from the DFU edge at the initial visit, using biopsy and debridement methods. Nuclear presence of c-myc and p-GR was quantified by immunohistochemistry, our recently developed SANDD algorithm and correlated to clinical outcomes at week 12. Complete healing was observed in 42/107 (39%) of participants, and 65/107 (61%) were considered non-healers. The distributions of baseline c-myc and p-GR between healed and not-healed DFUs by week 12 were not significantly different (p>0.025). Although the two tested biomarkers lacked significant predictability, this first DFC study, involving a national consortium of DFU centers, successfully created a unique resource of wound-related biomaterials and clinical outcomes, providing a platform for future biomarker discovery and validation. Robert S. Kirsner¹, Irena Pastar¹, Amy Krambrink², Hadar Lev-Tov¹, Jamie Burgess¹, Giselle Kolenic², Ivan Jozic¹, Paola Catanuto¹, Jelena Marjanovic¹, Teresa Jones³, Peter Song², Brian Schmidt⁴, Rodica Pop-Busui⁴, Crystal Holmes⁴, Catherine Spino², Marjana Tomic-Canic¹ 1. DFC Biomarker Analysis Unit, Wound Healing and Regenerative Medicine Research Program, Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, United States. 2. Data Coordinating Center of the DFC, University of Michigan, Ann Arbor, MI, United States. 3. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, United States. 4. Clinical Research Unit of the DFC, University of Michigan, Ann Arbor, MI, United States. Stem Cell Biology, Tissue Regeneration and Wound Healing