致癌相关环状RNA在慢性乙型肝炎病毒 感染者的表达及临床意义  

Expression and clinical significance of carcinoma-related circular RNA in patients with chronic hepatitis B virus infection

作　　者：钱舒然 谭婧文 王萌婕 张思航 杨镇英 何越峰 李晖[1,2] Qian Shuran;Tan Jingwen;Wang Mengjie;Zhang Sihang;Yang Zhenying;He Yuefeng;Li Hui(Department of Hepatology,Affiliated Hospital of Yunnan University/The Second People’s Hospital of Yunnan Province,Kunming 650021,China;Kunming Medical University,Kunming 650500,China)

机构地区：[1]云南大学附属医院/云南省第二人民医院肝病科,昆明市650021 [2]昆明医科大学,昆明市650500

出　　处：《中华实验和临床感染病杂志（电子版）》2021年第2期78-85,共8页Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition)

基　　金：云南省医疗卫生单位内设研究机构科研项目(No.2018NS0004)。

摘　　要：目的探讨致癌相关环状RNA(circ-ASXL1、circ-BRIP1、circ-CFLAR、circ-LPAR1以及circ-MORC3)在慢性乙型肝炎病毒(HBV)感染者的表达变化及临床意义。方法选择云南大学附属医院/云南省第二人民医院2019年5月至12月住院和门诊收治的100例HBV感染者,其中慢性乙型肝炎患者50例(CHB组),HBV携带者50例(HBV携带组),另选择同期50例体检者为健康对照组。采用逆转录-实时荧光定量PCR(qRT-PCR)法检测入组研究对象外周血白细胞内circ-ASXL1、circ-BRIP1、circ-CFLAR、circ-LPAR1和circ-MORC3相对表达水平。采用Spearman相关分析检验circ-ASXL1、circ-BRIP1、circ-CFLAR、circ-LPAR1、circ-MORC3与乙型肝炎病毒表面抗原(HBsAg)浓度、HBV DNA水平的相关性,并应用ROC曲线评估上述环状RNA对于区分CHB患者和HBV携带者的诊断价值。结果CHB组、HBV携带者组和健康对照组患者中circ-ASXL1(H=11.93、P=0.003)、circ-BRIP1(H=13.24、P=0.001)、circ-CFLAR(H=20.89、P<0.001)、circ-LPAR1(H=19.33、P<0.001)和circ-MORC3(H=14.81、P=0.001)表达差异均具有统计学意义。与健康对照组相比,CHB组患者circ-ASXL1(Z=-3.26、P=0.001)、circ-BRIP1(Z=-3.52、P<0.001)、circ-CFLAR(Z=-4.23、P<0.001)、circ-LPAR1(Z=-4.03、P<0.001)和circ-MORC3(Z=-3.76、P<0.001)表达水平显著升高,差异有统计学意义;而HBV携带者组的表达与健康对照组差异无统计学意义(P均>0.05)。CHB患者和HBV携带者的HBsAg浓度与circ-ASXL1(r=0.261、P=0.009)、circ-BRIP1(r=0.287、P=0.004)、circ-CFLAR(r=0.211、P=0.037)、circ-LPAR1(r=0.213、P=0.035)和circ-MORC3(r=0.237、P=0.019)的表达水平均呈正相关,而HBV DNA水平与circ-ASXL1(r=0.080、P=0.430)、circ-BRIP1(r=0.076、P=0.454)、circ-CFLAR(r=0.084、P=0.406)、circ-LPAR1(r=0.020、P=0.846)和circ-MORC3(r=0.070、P=0.492)的表达水平无相关性。circ-ASXL1、circ-BRIP1、circ-CFLAR、circ-LPAR1和circ-MORC3区分CHB患者和健康人群的ROC曲线下面积分别为0.69(95%CI:0.59~0.79)、0.70(95%CI:0.60~0.81)�Objective To investigate the differential expression of circular RNA,such as circ-ASXL1,circ-BRIP1,circ-CFLAR,circ-LPAR1 and circ-MORC3 in patients with chronic hepatitis B virus(HBV)infection and their clinical significance.Methods Total of 100 patients with HBV infection in Affiliated Hospital of Yunnan University/The Second People’s Hospital of Yunnan Province from May to December 2019 were selected,including 50 patients of chronic hepatitis B(CHB),50 HBV carriers and 50 healthy controls.Expressions of circ-ASXL1,circ-BRIP1,circ-CFLAR,circ-LPAR1 and circ-MORC3 in peripheral blood leukocytes of all subjects were detected by fluorescence real-time quantitative RT-PCR(qRT-PCR).The correlation between HBV surface antigen(HBsAg)concentration and HBV DNA level and expressions of circ-ASXL1,circ-BRIP1,circ-CFLAR,circ-LPAR1 and circ-MORC3 were analyzed by Spearman correlation analysis.The diagnostic value of these circular RNA in distinguishing between CHB patients and HBV carriers were evaluated by receiver operating characteristic(ROC)curve.Results The expressions of circ-ASXL1(H=11.93,P=0.003),circ-BRIP1(H=13.24,P=0.001),circ-CFLAR(H=20.89,P<0.001),circ-LPAR1(H=19.33,P<0.001)and circ-MORC3(H=14.81,P=0.001)between patients of CHB group,HBV carriers group and control group were significantly different.The expressions of circ-ASXL1(Z=-3.26,P=0.001),circ-BRIP1(Z=-3.52,P<0.001),circ-CFLAR(Z=-4.23,P<0.001),circ-LPAR1(Z=-4.03,P<0.001)and circ-MORC3(Z=-3.76,P<0.001)in CHB group were significantly higher than those in control group,while there were no significant difference between HBV carriers group and control group(all P>0.05).The HBsAg concentration had significantly positive relationship with expression levels of circ-ASXL1(r=0.261,P=0.009),circ-BRIP1(r=0.287,P=0.004),circ-CFLAR(r=0.211,P=0.037),circ-LPAR1(r=0.213,P=0.035),circ-MORC3(r=0.237,P=0.019)in CHB group and HBV carriers group,but there were no significant correlation between HBV DNA level and expression levels of circ-ASXL1(r=0.080,P=0.430),circ-BRIP1(r=0.07

关 键 词：肝炎 乙型 慢性 环状RNA 免疫调控 

分 类 号：R512.62[医药卫生—内科学]