微RNA-92a在系统性红斑狼疮血浆中的表达及临床意义

Detection of the plasma miR-92a expression in systemic lupus erythematosus and its clinic significance

目的分析微RNA（miR）-92a在SLE患者血浆中的表达及临床意义。方法收集44例SLE患者、16例RA患者和20名健康对照血浆标本，抽提血浆中小RNA，逆转录后，以cel-miR．39为外参，通过定量PCR检测血浆miR-92a的表达，通过实时荧光定量PCR和琼脂糖凝胶电泳对miR-92a和cel．miR-39的特异性分析；受试者工作特征曲线（ROC曲线）分析血浆miR-92a作为SLE诊断的敏感性和特异性。采用Mann．WhitneyU检验、Kruskal．Wallis检验、r检验和Pearson相关分析进行统计分析。结果miR．92a在SLE患者49．20（5．33，95．17）、健康者411．30（320．84，504．69）和RA患者25．59（11．20，30．54）血浆中的相对表达量差异有统计学意义（x2=40．77，P〈0．01）。与健康对照相比，SLE患者血浆中miR-92a表达水平明显下调（49．20和411．30，P〈0．01），RA患者血浆中miR-92a相对表达水平较健康人，也明显下调（25．59与411．30，P〈0．01）。SLE患者血浆miR-92a区分健康对照及RA患者血浆miR-92a区分健康对照的ROC曲线下面积（AUC）分别为0．958和1．00。血浆miR-92a表达水平以198．59区别SLE患者和健康对照的特异性和敏感性达90％，93．2％；以85．35临界值区别RA患者与健康对照的特异性和敏感性达100％和100％。血浆miR-92a的表达水平在低补体c3，高血肌酐、高血尿素氮，高ALT及高LDH的SLE患者进一步降低（P均〈o．05）。结论SLE患者血浆中下调表达的miR-92a可能与其发病和病情进展相关，是SLE及终末期肾功能损害临床诊断一个新的生物学指标。

Objective To analyze miR-92a expression and its clinical significance in the plasma of systemic lupus erythematosus （SLE） patients. Methods Plasma samples from 44 SLE patients, 16 rheumatoid arthritis （RA） patients and 20 healthy controls were collected. The small RNAs in these plasma samples were isolated and reversely transcribed. Using cel-miR-39 as the external reference, the levels of miR-92a expres- sion were detected by real-time polymerase chain reaction （PCR） method. MiR-92a and cel-miR-39 were analyzed by real-time fluorescence quantitative PCR and agarose gel electrophoresis. The sensitivity and specificity of miR-92a as SLE were analyzed by receiver-operating characteristic （ROC） curve. The correlation between the levels of miR-92a expression and the clinic pathological features of SLE and biological significance of miR-92a expression in SLE were further analyzed by Pearson or Chi-square test. Results Our data indicated that the plasma levels of miR-92a expression was 49.20 （5.33, 95.17） in SLE patients, 411.30 （320.84, 504.69）~in healthy controls, and 25.59（11.20,30.54） in RA patients. The difference was significant （V=40.77, P〈0.01）. The area under the ROC curve （AUC） was 0.958 for discriminating between SLE patients and normal subjects and 1.00 for discriminating between RA patients and healthy controls. The levels of miR- 92a expression cutoff values were set the as 198.59 for healthy control and 85.35 for RA patients, the diagnostie sensititity and specificity were 93.2%, 90%, and 100%, 100%, res-pectively. The analysis of the correlation between miR-92a expression and the clinic pathological features of SLE had shown that the levels of plasma miR-92a expressions were much lower in SLE patients with down-regulated complement C3, and up-regulated urea nitrogen, ereatinine, LDH, ATH （all P〈0.05）.Conclusion＂ D0wn-regulated＇ ~ mlR-92a＇ expression in plasma of SLE may be involved in the SLE disease occurrence or development and could be used as a novel potential diagnostic biomarker for SLE.