血清miR-192和miR-29a在肝硬化无创诊断中的应用价值

Value of Serum miR-192 and miR-29a for Non-invasive Diagnosis of Liver Cirrhosis

背景:早期诊断肝硬化并予早期干预可阻止病情进展,避免或延缓肝硬化失代偿发生。筛选血清学无创标记物是肝硬化临床诊断和评估研究的重要内容。目的:评价血清miR-192和miR-29a在肝硬化无创诊断中的应用价值。方法:通过文献检索和real-time PCR筛选验证发现在肝硬化患者血清中差异表达明显的miRNAs——miR-192和miR-29a,以real-time PCR检测两者在120例肝硬化患者和76名健康对照者血清中的表达水平;二元logistic回归建立两者联合检测诊断肝硬化的数学模型,ROC曲线评估诊断效能。结果:肝硬化组血清miR-192表达水平显著高于对照组,血清miR-29a表达水平则显著低于对照组(P<0.001)。由两者联合检测数学模型计算得到的风险评分诊断肝硬化的价值明显优于单一指标检测[ROC曲线下面积(AUC):0.968对0.887和0.933],且优于临床常用肝硬化血清学无创诊断指标APRI、FIB-4和ARR(AUC:0.796、0.793和0.571)。血清miR-192、miR-29a表达水平以及两者联合检测的风险评分与肝硬化Child-Pugh分级显著相关(P<0.05)。结论:miR-192、miR-29a以及两者联合检测的风险评分可作为肝硬化无创诊断和评估新的血清分子标记物。

Background: Diagnosis of liver cirrhosis in early stage with early intervention may stabilize disease progression,avoiding or delaying the occurrence of decompensation. Seeking non-invasive serum biomarkers is becoming an important topic in the diagnosis and assessment of liver cirrhosis. Aims: To study the value of serum miR-192 and miR-29 a as noninvasive biomarkers for the diagnosis of liver cirrhosis. Methods: Differentially expressed serum miRNAs between patients with liver cirrhosis and healthy controls were screened through online literature retrieval and then confirmed by real-time PCR. Serum levels of two confirmed miRNAs,miR-192 and miR-29 a were analyzed in 120 patients with liver cirrhosis and76 healthy volunteers by real-time PCR. A mathematical model of combined detection of miR-192 and miR-29 a for diagnosis of liver cirrhosis was established by binary logistic regression. The diagnostic performance of various non-invasive serum indicators was evaluated by ROC curve analysis. Results: Compared with healthy controls,expression level of serum miR-192 in cirrhotic patients was significantly increased and that of serum miR-29 a was significantly reduced( P < 0. 001).The diagnostic performance of risk score obtained from mathematical model of combined detection of serum miR-192 and miR-29 a was superior to that of single miRNA detection or other non-invasive serum indicators,such as APRI,FIB-4 and ARR,the areas under ROC curve of the above mentioned indicators were 0. 968,0. 887,0. 933,0. 796,0. 793,and0. 571,respectively. Serum levels of miR-192,miR-29 a and the risk score of their combined detection were significantly correlated with the stage of liver cirrhosis according to the Child-Pugh classification( P < 0. 05). Conclusions: Serum miR-192,miR-29 a and the risk score of their combined detection might be novel non-invasive biomarkers for the diagnosis and assessment of liver cirrhosis.