【摘要】 目的探讨分析外周血长链非编码RNA(lncRNA)-LET对慢性乙型肝炎(CHB)肝硬化的诊断价值,为肝硬化的早期临床诊断治疗提供依据。方法选取2017年3月-2019年5月在承德医学院附属医院就诊的CHB患者175例,其中乙型肝炎肝硬化患者52例(肝硬化组),无肝硬化病理改变患者123例(非肝硬化组),再选择同期在本院健康体检的40例健康人群作为正常对照组。检测各组受试者肝功能指标、外周血lncRNA-LET水平。计量资料两组间比较采用t检验;多组间比较采用方差分析,进一步两两比较采用LSD-t检验。计数资料组间比较采用χ2检验。等级资料组间比较采用Kruskal-Wallis H秩和检验。相关性分析采用Pearson相关性分析。采用受试者工作特征曲线(ROC曲线)分析外周血lncRNA-LET对肝硬化的预测价值。结果肝硬化患者以及非肝硬化患者血清肝功能指标TBil、总胆汁酸(TBA)、Alb以及ALT均显著高于正常对照组,而血清胆碱酯酶(ChE)显著低于正常对照组(P值均<0. 05);肝硬化患者血清肝功能指标TBil、TBA、Alb以及ALT均显著高于非肝硬化患者,血清ChE显著低于非肝硬化患者(P值均<0. 05)。肝硬化组与非肝硬化组患者外周血lncRNA-LET相对表达量显著低于正常对照组(P值均<0. 05),其中肝硬化患者外周血lncRNA-LET相对表达量明显低于非肝硬化患者(P <0. 05)。随着患者肝纤维化分期的增加,lncRNA-LET相对表达量显著降低(P <0. 05)。CHB患者外周血lncRNA-LET相对表达量与肝纤维化分期、TBil、TBA、Alb、ALT呈显著负相关关系(r值分别为-0. 352、-0. 372、-0. 364、-0. 410,P值均<0. 001),与ChE呈显著正相关关系(r=0. 340,P <0. 001)。ROC曲线分析外周血lncRNA-LET对肝硬化的预测价值,结果显示ROC曲线下面积为0. 934,最佳截断值为0. 833,敏感度为84. 57%,特异度为80. 57%。结论外周血lncRNA-LET随着CHB肝纤维化进程的发展,其表达水平有所降低,且对CHB肝硬化具有较好的诊断价值,可成为肝硬化诊断的潜在生物学指标。更多还原

【Abstract】 Objective To investigate the value of peripheral blood long non-coding RNA-LET( lncRNA-LET) in the diagnosis of chronic hepatitis B( CHB) cirrhosis,and to provide a basis for early clinical diagnosis and treatment of liver cirrhosis. Methods A total of 175 CHB patients who attended The Affiliated Hospital of Chengde Medical University from March 2017 to May 2019 were enrolled,among whom52 patients with hepatitis B cirrhosis were enrolled as cirrhosis group and 123 patients without the pathological changes of liver cirrhosis were enrolled as non-cirrhosis group. A total of 40 healthy individuals who underwent physical examination in our hospital during the same period of time were enrolled as normal control group. Liver function parameters and the level of lncRNA-LET in peripheral blood were measured for all subjects. The t-test was used for comparison of continuous data between two groups; an analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups,and the Kruskal-Wallis H test was used for comparison of ranked data. A Pearson correlation analysis was performed to investigate correlation. The receiver operating characteristic( ROC) curve was used to investigate the value of peripheral blood lncRNA-LET in predicting liver cirrhosis. Results Compared with the normal control group,the cirrhosis group and the non-cirrhosis group had significantly higher serum levels of the liver function parameters total bilirubin( TBil),total bile acid( TBA),albumin( Alb),and alanine aminotransferase( ALT)( all P < 0. 05) and a significantly lower serum level of cholinesterase( ChE)( P < 0. 05); compared with the non-cirrhosis group,the cirrhosis group had significantly higher serum levels of TBil,TBA,Alb,and ALT( all P < 0. 05) and a significantly lower serum level of ChE( P < 0. 05). Compared with the normal control group,the cirrhosis group and the non-cirrhosis group had significantly lower relative expression of lncRNA-LET in peripheral blood( P < 0. 05),and the cirrhosis group had significantly lower relative expression of lncRNA-LET in peripheral blood than the non-cirrhosis group( P < 0. 05). The relative expression of lncRNA-LET decreased significantly with the increase in liver fibrosis stage( P < 0. 05). In the patients with CHB,the relative expression of lncRNA-LET in peripheral blood was negatively correlated with liver fibrosis stage,TBil,TBA,Alb,and ALT( r =-0. 352,-0. 372,-0. 364,and-0. 410,all P < 0. 001) and was positively correlated with ChE( r = 0. 340,P < 0. 001). The ROC curve was used to analyze the value of peripheral blood lncRNA-LET in predicting liver cirrhosis,and the area under the ROC curve was 0. 934,with an optimal cut-off value of 0. 833,a sensitivity of 84. 57%,and a specificity of 80. 57%. Conclusion The expression level of lncRNA-LET in peripheral blood decreases with the progression of liver fibrosis and has a good value in the diagnosis of CHB cirrhosis,and therefore,it can be used as a potential biological indicator for the diagnosis of liver cirrhosis.更多还原