• Br J Surg · Jul 2019

    Development and validation of a gene expression test to identify hard-to-heal chronic venous leg ulcers.

    • D C Bosanquet, A J Sanders, F Ruge, J Lane, C A Morris, W G Jiang, and K G Harding.
    • Clinical Innovation Hub, Cardiff University, Cardiff, UK.
    • Br J Surg. 2019 Jul 1; 106 (8): 1035-1042.

    BackgroundChronic venous leg ulcers pose a significant burden to healthcare systems, and predicting wound healing is challenging. The aim of this study was to develop a genetic test to evaluate the propensity of a chronic ulcer to heal.MethodsSequential refinement and testing of a gene expression signature was conducted using three distinct cohorts of human wound tissue. The expression of candidate genes was screened using a cohort of acute and chronic wound tissue and normal skin with quantitative transcript analysis. Genes showing significant expression differences were combined and examined, using receiver operating characteristic (ROC) curve analysis, in a controlled prospective study of patients with venous leg ulcers. A refined gene signature was evaluated using a prospective, blinded study of consecutive patients with venous ulcers.ResultsThe initial gene signature, comprising 25 genes, could identify the outcome (healing versus non-healing) of chronic venous leg ulcers (area under the curve (AUC) 0·84, 95 per cent c.i. 0·73 to 0·94). Subsequent refinement resulted in a final 14-gene signature (WD14), which performed equally well (AUC 0·88, 0·80 to 0·97). When examined in a prospective blinded study, the WD14 signature could also identify wounds likely to demonstrate signs of healing (AUC 0·73, 0·62 to 0·84).ConclusionA gene signature can identify people with chronic venous leg ulcers that are unlikely to heal.© 2019 BJS Society Ltd Published by John Wiley & Sons Ltd.

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