Evaluation of c-Myc and Phosphorylated Glucocorticoid Receptor (p-GR) for Predicting Diabetic Foot Ulcer Healing-A...

Diabetic foot ulcers (DFUs) are a serious clinical problem, leading to high rates of morbidity, disability, amputations, and mortality. Many DFUs fail to heal completely and a major challenge includes identifying non-healers early in treatment. However, effective predictive biomarkers for DFUs have not yet been validated. The goal of this study was to validate if two previously identified, objective and quantitative tissue biomarkers, c-Myc and phosphorylated glucocorticoid receptor (p-GR), could predict complete healing at week 12 in a multicenter observational cohort study of individuals with open DFUs, conducted by the NIDDK Diabetic Foot Consortium (DFC). Wound tissue collected at the initial visit was analysed for c-Myc and p-GR biomarkers by immunohistochemistry, quantifying their nuclear presence in full thickness epidermis and correlating with week 12 clinical outcomes. The primary analyses included AUC comparisons to assess the biomarkers' predictive capability for wound healing. Other analyses included descriptive measures and t-tests to evaluate the difference between biomarker quantification among healers and non-healers. Of 140 DFUs enrolled, 107 participants completed biomarker and clinical outcome data for analysis. The distributions of baseline c-Myc and p-GR between healed and not-healed DFUs by week 12 were not significantly different (p > 0.05). Although the two biomarkers did not yield significant predictability (ΔAUC = -0.006, 95% CI (-0.02, 0.01) and ΔAUC = -0.0002, 95% CI (-0.01, 0.01), p > 0.025) for each of c-Myc and p-GR respectively, this first DFC clinical study using a national consortium of DFU centres successfully created a unique resource of wound-related biomaterials coupled with the clinical outcomes, providing a platform for further biomarker discovery and validation.