Bustamante Alejandro, Mancha Fernando, Macher Hada C, García-Berrocoso Teresa, Giralt Dolors, Ribó Marc, Guerrero Juan M, Montaner Joan
Neurovascular Research Laboratory, Institut de Recerca, Hospital Universitari Vall d'Hebron. Universitat Autonoma de Barcelona, Barcelona, Spain.
Stroke Program, Institute of Biomedicine of Seville, Hospital Universitario Virgen del Rocio, Seville, Spain.
J Circ Biomark. 2016 Sep 26;5:1849454416668791. doi: 10.1177/1849454416668791. eCollection 2016 Jan-Dec.
Circulating cell-free DNA (cfDNA) has been described as a prognostic marker for several diseases. Its prognostic value for short-term outcome in stroke patients treated with intravenous thrombolysis remains unexplored. cfDNA was measured on admission in 54 tissue plasminogen activator (tPA)-treated patients and 15 healthy controls using a real-time quantitative polymerase chain reaction assay. Neurological outcome was assessed at 48 h. Predictors of neurological improvement were evaluated by logistic regression analysis, and the additional predictive value of cfDNA over clinical variables was determined by integrated discrimination improvement (IDI). Stroke patients presented higher baseline cfDNA than healthy controls (408.5 (179-700.5) vs. 153.5 (66.9-700.5) kilogenome-equivalents/L, = 0.123). A trend towards lower cfDNA levels was found in patients who neurologically improved at 48 h (269.5 (143.3-680) vs. 504 (345.9-792.3) kilogenome-equivalents/L, = 0.130). In logistic regression analysis, recanalization at 1 h and cfDNA < 302.75 kilogenome-equivalents/L was independently associated with neurological improvement after adjustment by age, gender and baseline National Institutes of Health Stroke Scale score. The addition of cfDNA to the clinical predictive model improved its discrimination (IDI = 21.2% (9.2-33.3%), = 0.009). These data suggest that cfDNA could be a surrogate marker for monitoring tPA efficacy by the prediction of short-term neurological outcome.
循环游离DNA(cfDNA)已被描述为多种疾病的预后标志物。其对接受静脉溶栓治疗的中风患者短期预后的价值尚未得到探索。使用实时定量聚合酶链反应分析法对54例接受组织型纤溶酶原激活剂(tPA)治疗的患者和15名健康对照者入院时的cfDNA进行了测量。在48小时时评估神经功能结局。通过逻辑回归分析评估神经功能改善的预测因素,并通过综合判别改善(IDI)确定cfDNA相对于临床变量的额外预测价值。中风患者的基线cfDNA高于健康对照者(408.5(179 - 700.5)对153.5(66.9 - 700.5)千基因组当量/L,P = 0.123)。在48小时神经功能改善的患者中发现cfDNA水平有降低趋势(269.5(143.3 - 680)对504(345.9 - 792.3)千基因组当量/L,P = 0.130)。在逻辑回归分析中,调整年龄、性别和基线美国国立卫生研究院卒中量表评分后,1小时再通和cfDNA < 302.75千基因组当量/L与神经功能改善独立相关。将cfDNA添加到临床预测模型中可改善其判别能力(IDI = 21.2%(9.2 - 33.3%),P = 0.009)。这些数据表明,cfDNA可能是通过预测短期神经功能结局来监测tPA疗效的替代标志物。