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血浆微RNA-126表达水平对银屑病患者阿维A、甲氨蝶呤联合光疗应答的预测价值
金曌,程杨,苏慧,张峻,付霆*
0
(武汉市第一医院皮肤科, 武汉 430022
*通信作者)
摘要:
目的 探索接受阿维A、甲氨蝶呤联合光疗治疗的银屑病患者血浆微RNA-126(miRNA-126)表达水平在治疗前后的变化及其对于疗效的预测作用。方法 连续纳入196例接受阿维A、甲氨蝶呤联合紫外线光疗治疗的中重度银屑病患者作为研究对象,并纳入同期200名健康志愿者作为对照。分别于基线期及治疗1个月、3个月和6个月后采集银屑病患者的血液样本,在入组后采集健康受试者的血液样本,测量血浆miRNA-126表达水平。采用银屑病皮损面积及严重度指数(PASI)评估疾病严重程度,PASI 50应答(治疗后PASI与基线期相比下降50%)和PASI 75应答(治疗后PASI与基线期相比下降75%)评估治疗效果。采用Spearman等级相关检验分析患者血浆miRNA-126表达水平与PASI的相关性,受试者工作特征(ROC)曲线评估miRNA-126相对表达量对银屑病的诊断价值,单因素和多因素logistic回归模型分析PASI 50和PASI 75应答的影响因素。结果 基线期银屑病患者血浆中miRNA-126呈低表达,其表达水平与患者PASI呈负相关(r=-0.222,P=0.002)。ROC曲线分析结果显示血浆miRNA-126表达水平可以较好地分辨银屑病患者与健康对照(曲线下面积为0.700)。治疗1个月、3个月和6个月后,银屑病患者血浆miRNA-126表达水平均比基线期增高(P<0.01),PASI 50应答率分别为7.1%(14/196)、37.2%(73/196)及64.8%(127/196),PASI 75应答率分别为1.5%(3/196)、14.3%(28/196)及35.7%(70/196)。PASI 50应答和PASI 75应答患者基线期血浆miRNA-126相对表达量高于未应答患者(P<0.05)。Logistic回归分析结果显示基线期血浆miRNA-126相对表达量与患者PASI 50应答和PASI 75应答独立负相关。结论 银屑病患者血浆miRNA-126表达水平在接受阿维A、甲氨蝶呤联合紫外线光疗治疗后逐渐升高,且其基线期表达水平与治疗效果独立负相关。
关键词:  微RNA-126  银屑病  治疗应答  阿维A  甲氨蝶呤  紫外线疗法
DOI:10.16781/j.0258-879x.2019.10.1111
投稿时间:2019-03-11修订日期:2019-09-18
基金项目:
Predictive value of plasma microRNA-126 for treatment response of psoriasis patients to combined treatment with acitretin, methotrexate and ultraviolet phototherapy
JIN Zhao,CHENG Yang,SU Hui,ZHANG Jun,FU Ting*
(Department of Dermatology, The First People's Hospital of Wuhan, Wuhan 430022, Hubei, China
*Corresponding author)
Abstract:
Objective To investigate the plasma microRNA-126 (miRNA-126) level in psoriasis patients before and after acitretin, methotrexate and ultraviolet phototherapy-combined treatment, and to assess its value in predicting the treatment outcomes. Methods A total of 196 patients with moderate-to-severe psoriasis were consecutively enrolled and received combined treatment with acitretin, methotrexate and ultraviolet phototherapy, and 200 volunteers were recruited as healthy controls. Plasma samples of psoriasis patients were collected and miRNA-126 level was detected at baseline and after treatment for 1 month, 3 months and 6 months. Psoriasis area and severity index (PASI) were used to assess the disease severity. Treatment response was determined by PASI 50 response (PASI decreased by 50% compared with the baseline) and PASI 75 response (PASI decreased by 75% compared with the baseline). Spearman correlation test was used to analyze the correlation between the expression level of plasma miRNA-126 and PASI. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of relative expression of miRNA-126 in psoriasis patients. Univariate and multivariate logistic regression models were used to analyze the influencing factors of PASI 50 and PASI 75 responses. Results Baseline miRNA-126 expression was significantly lower in psoriasis patients compared with healthy controls and was negatively correlated with PASI score (r=-0.222,P=0.002). ROC curve displayed that miRNA-126 had a good diagnostic value for psoriasis (area under curve:0.700). After treatment for 1 month, 3 months and 6 months, miRNA-126 levels were significantly elevated compared with the baseline (P<0.01). The response rates of PASI 50 were 7.1% (14/196), 37.2% (73/196) and 64.8% (127/196) after treatment for 1 month, 3 months and 6 months, and those of PASI 75 were 1.5% (3/196), 14.3% (28/196) and 35.7% (70/196), respectively. PASI 50 and PASI 75 responders presented lower baseline miRNA-126 level (P<0.05). Logistic regression analysis revealed that baseline miRNA-126 level was negatively associated with PASI 50 and PASI 75 responses. Conclusion Plasma miRNA-126 level gradually increases in psoriasis patients after acitretin, methotrexate and ultraviolet phototherapy-combined treatment, and the baseline miRNA-126 level is negatively correlated with treatment response.
Key words:  microRNA-126  psoriasis  treatment response  acitretin  methotrexate  ultraviolet therapy