Transcriptomics in Venous Leg Ulcers (VLU): A Systematic Review

Venous leg ulcers (VLUs) are chronic wounds in the lower limbs that cause significant morbidity. The underlying biology underpinning non-healing in VLUs is still poorly understood and differences in transcriptomic profiles may help elucidate biological pathways involved in wound chronicity. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Studies were included if transcriptomes from adults with confirmed VLU were described. A search of EMBASE, OVID and PubMed between 1 January 1994 and 17 August 2024 yielded 429 articles; 34 studies were included after full-text screening by two independent reviewers. Twenty-nine studies investigated coding messenger RNA (mRNA) expression, while five studies investigated non-coding RNA. Samples were obtained from wound biopsies (n = 31) or whole blood (n = 3). There were variations in mRNA expression across comparisons between patients with VLUs and controls such as tissue from other patients, tissue from different sites and treated tissues. Altered levels of mRNA transcripts suggest chronic inflammatory states, hyperproliferation and reduced wound healing. Studies exploring non-coding RNAs described their roles in regulating wound repair. Paired analyses of microRNA expression demonstrate impact on RNA expression profiles, with effects on inhibition of wound healing. Transcriptomic analysis provides new insights into the pathophysiology of the development and healing of VLUs. Further development of RNA biomarkers and gene expression profiles can improve diagnosis and prognostication of VLUs, but heterogeneity of current data may make it difficult to draw clinical significance. Trial Registration: PROSPERO: CRD42024580526.