血浆miR-205在乙肝病毒相关肝脏疾病中的表达及其作为乙肝病毒所致肝细胞癌诊断标志物的价值  

Differential Expression of Plasma miR-205 in HBV-Related Liver Diseases and Diagnostic Potential for HBV-Induced Hepatocellular Carcinoma

作　　者：陈珊珊[1] 陈浩[1] 高珊珊[1] 周虎[1] 邱石黎[1] 喻明霞[1] 涂建成[1] 

机构地区：[1]武汉大学中南医院检验科/基因诊断中心,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2016年第3期445-450,共6页Medical Journal of Wuhan University

基　　金：国家重点基础研究发展计划(973计划)资助项目(编号:2012CB720605)

摘　　要：目的:探讨microRNA-205(miR-205)在乙型肝炎(乙肝)病毒(HBV)相关肝脏疾病患者血浆中的表达水平及其作为乙肝病毒所致肝细胞癌早期诊断标志物的潜在价值。方法:选取56例健康人群、63例慢性乙肝患者(CHB)、59例乙肝肝硬化患者(HBV-LC)及64例乙肝肝细胞癌患者(HBV-HCC),采用实时荧光定量PCR技术验证miR-205在4组人群血浆中的表达差异水平及其诊断效能。结果:miR-205在HBV-HCC患者血浆中的表达水平明显低于健康人群及HBV-LC组,P值均小于0.001,而与CHB组相比则无显著统计学差异(P=0.921)。受试者工作特征(ROC)曲线分析显示血浆miR-205对鉴别诊断HBV-HCC与健康人群、HBV-LC具有重要的意义,曲线下面积(AUC)分别为0.885(敏感性:96.9%,特异性:67.9%)和0.781(敏感性:96.9%,特异性:54.2%)。并且,血浆miR-205联合甲胎蛋白(AFP)在HBV-HCC与HBV-LC的鉴别中AUC及特异性可明显得到提高。进一步研究发现,血浆miR-205在从AFP<400ng/ml的HBV-HCC、HBV-LC患者中鉴别出HBV-HCC的AUC为0.815,敏感性为100%,明显优于AFP。结论:血浆miR-205虽然不能鉴别CHB与HBV-HCC,但其作为标志物应用于HBV-HCC的早期诊断,尤其是监控由乙肝肝硬化发展至肝细胞癌过程的潜在价值是不可忽视的。Objective：To investigate the differential expression of plasma miR-205 in HBV-related liver diseases,and its clinical significance in diagnosing HBV-induced HCC.Methods：Plasma samples of 56 healthy subjects,59 patients with chronic hepatitis B（CHB）,56 cases of HBV-related liver cirrhosis（HBV-LC）,64 cases of HBV-induced HCC（HBV-HCC）were collected and analyzed using quantitative real-time PCR.Results：The expression levels of plasma miR-205 were markedly decreased in HBV-HCC patients compared with healthy subjects and HBV-LC patients,both P〈0.001.Whereas,no statistical difference was observed between HBV-HCC and CHB（P =0.921）.The receiver operating characteristic（ROC）curve analyses indicated that plasma miR-205 exhibited promising diagnostic value for differentiating HBV-HCC from healthy subjects andHBV-LC patients,the area under the ROC curves（AUCs）were 0.885（Sensitivity：96.9%,Specificity：67.9%）and 0.781（Sensitivity：96.9%,Specificity：54.2%）,respectively.Moreover,the AUC and specificity would be improved by combining this miRNA with serum AFP.Furthermore,we found that HBV-HCC patients who underwent a low level of serum AFP（AFP400ng/ml）could be indentified from HBV-LC patients by plasma miR-205 with a high sensitivity（100%）and AUC（0.815）.Conclusion：Although plasma-based miR-205 holds no promise as a diagnostic biomarker for differentiating HBV-HCC from CHB,the potential value for HBVHCC early diagnosis,especially for those HBV-HCCs derived from HBV-LC is noticeable.

关 键 词：血浆miRNA miR-205 慢性乙型肝炎 乙肝肝硬化 乙肝肝细胞癌 标志物 

分 类 号：R735.7[医药卫生—肿瘤]