Leveraging urinary microRNAs as systemic biomarkers for dermatologic diseases: Non-invasive prediction of diabetic foot ulcer healing

Summary: Abstract Body: Skin inflammation releases short, stable non-coding microRNAs (miRNAs) into circulation, and miRNAs from extra-cutaneous tissues can target the skin. As such, systemic miRNAs are attractive prognostic and therapeutic biomarkers for dermatologic disease, particularly when captured non-invasively in patient urine. To this end, a robust amplification-free method was developed to profile urinary miRNAs in diabetic foot ulcer (DFU) individuals, aiming to identify early miRNA predictors of DFU healing outcomes (healed or not healed) 12 weeks after initial clinical presentation. MiRNAs were successfully profiled in a pilot cohort of 55 DFU individuals at enrollment in the NIDDK Diabetic Foot Consortium, normalized to urine quantity and concentration, and subjected to combined data reduction and prognostic modeling. Using this approach, a multi-miRNA biomarker was successfully identified that predicted DFU healing outcome 12 weeks after study enrollment with a sensitivity of 86%, specificity of 79%, and an aROC of 0.8. In this pilot cohort, the miRNA biomarker outperformed clinical risk factors known to be linked to non-healing DFUs, including wound area, race, and renal function, and is undergoing further validation in an expanded cohort. The methods and modeling approaches utilized in this study can profile urinary miRNAs from a spectrum of skin diseases, with the goal of developing non-invasive prognostic and therapeutic biomarkers for clinical outcomes to improve the lives of people with dermatologic disease. Sophie M. Bilik¹, Lindsey Siegfried², Clement David³, Vivien Chen⁴, David J. Margolis⁵, Irena Pastar¹, Marjana Tomic-Canic¹, Rivka Stone¹ 1. Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, United States. 2. University of Cincinnati College of Medicine, Cincinnati, OH, United States. 3. Bruker Spatial Biology, Seattle, WA, United States. 4. Dermatology, Tulane Medical Center, New Orleans, LA, United States. 5. Dermatology & Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States. Translational Studies: Preclinical