Primary analyses: c-Myc (A) and p-GR (B) nuclear presence shows unremarkable difference between non-healing and healed patients. Representative images of immunoperoxidase staining of the cellular Myc (c-Myc) and phosphorylated glucocorticoid receptor (p-GR) of diabetic foot ulcer tissue are shown. The numbers above the images indicate % of positive nuclear staining for each biomarker. Dashed line indicates the basement membrane. Scale bar = 200 μM. Boxplots show similar distributions of baseline c-Myc and p-GR quantifications between healed and non-healed DFUs at week 12. Median baseline c-Myc was numerically higher in the healed group whereas median baseline of p-GR was numerically higher in not-healed group. Boxplot symbols: Diamond = mean, middle line = median, bottom box line = first quartile (Q1), top box line = third quartile (Q3), whiskers are 1.5*IQR from Q1 to Q3. Credit: Wound Repair and Regeneration (2025). DOI: 10.1111/wrr.70044

Diabetic foot ulcers (DFUs) are a major clinical challenge, with high rates of morbidity, disability, amputations and mortality. Despite extensive research, effective predictive biomarkers for DFUs healing remain elusive.

A new study led by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diabetic Foot Consortium (DFC) and published in Wound Repair and Regeneration evaluated the potential of two biomarkers, c-myc and phosphorylated-glucocorticoid receptor (p-GR), in wound tissue to predict healing outcomes in DFUs.

The study represents an important initial step in identifying biomarkers that can predict clinical outcomes, monitor progress or predict recurrence. The research also revealed critical insights into the challenges faced in managing this complex medical condition.

Most importantly, the study created a valuable resource of wound-related biological samples coupled with comprehensive clinical data to support ongoing and future studies aimed at identifying new DFU biomarkers.

The study evaluated wound tissue collected at baseline from 107 participants with active DFUs and assessed the nuclear presence of c-myc and phosphorylated-glucocorticoid receptor (p-GR) via immunohistochemistry. While mean biomarker levels were similar between ulcers that healed and those that persisted, p-GR levels aligned with the study's hypothesis, suggesting avenues for further investigation.

The clinical study was the DFC's first and successfully demonstrated the feasibility of integrating tissue biomarker analysis into prospective DFU research. The effort resulted in a unique, well-characterized biorepository of wound tissue samples linked to clinical outcomes, which will serve as a critical platform for future discovery and validation of predictive markers.

"This study lays the groundwork for further biomarker discovery and advancing DFU science and clinical practice, " said the University of Miami Miller School of Medicine's Marjana Tomic-Canic, Ph.D., Professor of Dermatology at the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Director of the Wound Healing and Regenerative Medicine Research Program and the lead investigator of the DFC's University of Miami Biomarker Analyses Unit.

"Although there is still work to be done to develop biomarkers that are strong predictors of healing, the established infrastructure of the DFC is leading the way and will be crucial for supporting research focused on DFU healing."

The DFC's ongoing efforts to expand this biorepository, combined with advanced technologies like spatial transcriptomics and proteomics, offer new opportunities to uncover novel biomarkers and improve DFU management. The study reinforces the DFC's commitment to advancing DFU science with its master protocol, "No DFU Patient Goes Unstudied, " ensuring the research is generalizable to all individuals burdened by DFUs.

"This effort represents a critical resource for continued biomarker exploration. We are now in a stronger position to further investigate other molecules and technologies that may lead to reliable, predictive tests for DFU healing, " said Dr. Tomic-Canic. "This study is just the beginning, and the resources generated will continue to drive the advancement of DFU research for years to come."

More information: Robert S. Kirsner et al, Evaluation of c‐Myc and Phosphorylated Glucocorticoid Receptor (p‐GR) for Predicting Diabetic Foot Ulcer Healing—A Diabetic Foot Consortium Study, Wound Repair and Regeneration (2025). DOI: 10.1111/wrr.70044