Development and validation of a gene expression test to identify hard-to-heal chronic venous leg ulcers
Development and validation of a gene expression test to identify hard-to-heal chronic venous leg ulcers
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DOI：
10.1002/bjs.11161
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发表时间：
2019-07-01
影响因子：
9.6
通讯作者：
Harding, K. G.
中科院分区：
文献类型：
--
作者：
Bosanquet, D. C.;Sanders, A. J.;Harding, K. G.
背景：慢性下肢静脉溃疡给医疗保健系统带来了巨大的负担，预测伤口愈合具有挑战性。本研究的目的是开发一种基因测试，以评估的倾向，慢性溃疡health.Methods：顺序细化和测试的基因表达签名进行了使用三个不同的队列的人类伤口组织。使用一组急性和慢性伤口组织和正常皮肤的定量转录分析来筛选候选基因的表达。在下肢静脉性溃疡患者的前瞻性对照研究中，采用受试者工作特征（ROC）曲线分析，对显示显著表达差异的基因进行合并和检查。一个完善的基因签名进行了评估，使用前瞻性，盲法研究连续患者静脉ulcers.Results：最初的基因签名，包括25个基因，可以确定的结果（愈合与不愈合）慢性静脉腿部溃疡（曲线下面积（AUC）0.84，95% c。I. 0-73 0-94）。随后的改进产生了最终的14个基因标签（WD 14），其表现同样良好（AUC 0-88、0-80至0-97）。当在前瞻性盲法研究中进行检查时，WD 14签名也可以识别可能显示愈合迹象的伤口（AUC 0.73，0-62至0.84）。结论：基因签名可以识别患有慢性下肢静脉溃疡的人，这些溃疡不太可能愈合。
Background: Chronic 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.Methods: Sequential 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.Results: The 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 (WD 14), 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).Conclusion: A gene signature can identify people with chronic venous leg ulcers that are unlikely to heal.