A gene signature of nonhealing venous ulcers: Potential diagnostic markers

doi:10.1016/j.jaad.2008.07.018

Journal of the American Academy of Dermatology

Volume 59, Issue 5, November 2008, Pages 758-771

https://doi.org/10.1016/j.jaad.2008.07.018 Get rights and content

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.

Section snippets

Participants

Patients were recruited according to a protocol approved by the our institutional review board. Consent was obtained from all patients, and Declaration of Helsinki protocols were followed. In all, 5 patients with nonhealing and 5 patients with healing chronic venous leg ulcers as defined by previous prognostic models for wound healing in venous leg ulcers were studied.17, 18 All ulcers were present for at least 4 weeks. Healing venous leg ulcers were defined as ulcers that were less than 5 cm²

Gene expression profile of healing versus nonhealing epidermal wound edge

Table I, Table II demonstrate the top 15 genes that were differentially expressed between the two groups of venous leg ulcers from the keratinocytes of the tissue sampled at the nonhealing wound edge. The most striking finding in this data set is the extent to which genes implicated in epidermal hyperproliferation and tissue repair were differentially expressed. Of additional interest is that the down-regulation (>250.00) demonstrated in the nonhealing wound edges was much greater than the

Discussion

Optimal wound healing depends on the concerted interplay of thousands of genes. Of those identified to be differently expressed between these two groups of venous leg ulcers, several specific genes deserve special mention.

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: Supported by the Department of Dermatology at the University of Miami and by the by National Institutes of Health grants NR008029 and AG030673, and a pilot award (UL1RR024996) from the Center for Translational Science Award of the Weill Cornell Medical College.

: Conflicts of interest: None declared.

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ReportA gene signature of nonhealing venous ulcers: Potential diagnostic markers

Background

Objective

Methods

Results

Limitations

Conclusions

Section snippets

Participants

Gene expression profile of healing versus nonhealing epidermal wound edge

Discussion

J Vasc Surg

J Vasc Surg

J Invest Dermatol

Am J Surg

Am J Pathol

Am J Med

J Am Acad Dermatol

Lab Invest

Toxicol Appl Pharmacol

Ann Biochem

Invest Dermatol

Invest Dermatol

Mol Immunol

J Invest Dermatol

J Invest Dermatol

Exp Cell Res

J Dermatol Sci

Chronic venous insufficiency and venous leg ulceration

J Am Acad Dermatol

Healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent

Arch Dermatol

Successful methods of treating venous ulcers: the tried and true, plus the novel and new

Postgrad Med

Report
A gene signature of nonhealing venous ulcers: Potential diagnostic markers