A gene signature of nonhealing venous ulcers: Potential diagnostic markers

Background: Venous leg ulcers are responsible for more than half of all lower extremity ulcerations. Significant interest has been focused on understanding the physiologic basis on which patients fail to heal with standard therapy. Objective: This study uses complementary DNA microarray analysis of tissue samples from healing and nonhealing venous leg ulcers to identify the genetic expression profiles from these dichotomous populations. Methods: Ulcer size and chronicity, factors that have been identified as prognostic indicators for healing, were used to distribute venous leg ulcers as healing versus nonhealing. Punch biopsy samples were obtained from the wound edge and wound bed of all venous leg ulcers. The top 15 genes with differential expression greater than 2-fold between the two populations of wounds (P < .05) were reported. Results: Significant differences were demonstrated in the expression of a diverse collection of genes, with particular differences demonstrated by genes coding for structural epidermal proteins, genes associated with hyperproliferation and tissue injury, and transcription factors. Limitations: Small sample size may mitigate potential clinical implications of findings. Conclusions: The genetic expression profiles displayed here may have implications for the development of novel therapies for chronic venous leg ulcers, and may also serve as prognostic indicators for wound healing. (J Am Acad Dermatol 2008;59:758-71.)