血清miR-483-5p是感染HBV基本核心启动子双突变(A1762T,G1764A)株人群潜在肝癌高危标记物  

Serum miR-483-5p as a potential marker to differentiate hepatocellular carcinoma(HCC) from individuals infected with HBV with basal core promoter double mutations(A1762T, G1764A)

作　　者：王超[1] 彭涛[2] 陈钦艳[1] 胡莉萍[1] 王学燕[1] 任创创 杨庆利[1] 陈茂伟[3] 方钟燎[1] 宋贵生 

机构地区：[1]广西壮族自治区疾病预防控制中心广西病毒性肝炎防治研究重点实验室,广西南宁530028 [2]广西医科大学第一附属医院肝胆外科 [3]广西医科大学第一附属医院感染性疾病科 [4]明尼苏达大学医学院

出　　处：《应用预防医学》2018年第1期1-5,共5页Applied Preventive Medicine

基　　金：美国明尼苏达大学种子项目;国家自然科学基金项目(81260439/H2609)1984

摘　　要：目的探索同为感染HBV基本核心启动子(BCP)双突变病毒株的肝细胞癌(HCC)患者和HBs Ag无症状携带者血清中差异表达的miRNA。方法采用病例对照研究方法,分初筛阶段(miRNA测序)和验证阶段(q RTPCR),筛选组间差异表达的miRNA。初筛阶段招募HCC病例组18人,HBs Ag无症状携带者对照组25人;验证阶段招募200名研究对象,包括1个病例组(39人)和4个对照组(161人)。结果初筛阶段共发现58条差异表达的miRNA,包括39条已知的miRNA和19条新的miRNA。选择7条与肝脏疾病有关的miRNA进行验证,结果发现3条miRNA得到证实。miR-483-5p的ROC曲线下面积(AUC)有最大值(0.815,95%CI:0.750~0.880),若将诊断肝癌阈值设为6.7,其敏感性、特异性分别为89.5%、61.1%;将AFP诊断肝癌阈值设在20.8 ng/m L,AFP的敏感性、特异性分别为61.5%、92.0%。miR-483-5p的表达水平在感染HBV BCP双突变病毒株的无症状携带者组与HBs Ag阴性组间的差异没有统计学意义,但在感染BCP双突变病毒株的无症状携带者组与HCC患者组之间差异有统计学意义(P<0.05)。结论将miR-483-5p与AFP联合使用可提高AFP诊断HCC的敏感性。miR-483-5p可能作为进一步缩小用标记物BCP双突变筛查出来作为肝癌监测的高危人群范围的标记物。Objective To identify differentially-expressed miRNAs between HCC cases and controls, among those infected with HBV with BCP double mutations. Methods A case-control study including discovery stage(miRNA sequencing) and validation stages(q RT-PCR) were performed. Study subjects in discovery study included 18 HCC cases and 25 asymptomatic HBs Ag carriers. In validation study, 200 study subjects were recruited, including 1 case group(n=39) and 4 control groups(n=161).Results The differential expression levels of 58 miRNAs were found to reach significantly differences in discovery stage, including 39 miRNAs being in Mi Rbase and 19 new miRNAs. Seven of the known miRNAs were selected for validation. Three of them were confirmed.The area under the ROC curve(AUC) of miR-483-5 p was highest(0.815, 95% CI:0.750—0.880). At the cut-off value of 6.7, the sensitivity and specificity of serum miR-483-5 p for HCC prediction were 89.5%, 61.1% while at the cut-off value of20.8 ng/m L, the sensitivity and specificity of serum AFP for HCC prediction were 61.5%, 92.0%. The expression levels of miR-483-5 p in asymptomatic BCP double mutations carrier group was not significantly different from that in HBs Ag negative group but different from that in HCC patients with BCP double mutations(P<0.05). Conclusions Combination of miR-483-5 p and AFP may increase the sensitivity of AFP in detection of HCC. miR-483-5 p may be a potential biomarker to narrow down further the subset identified with BCP double mutations for surveillance for HCC.

关 键 词：肝细胞癌(HCC) miRNA 差异表达 HBV 基本核心启动子 

分 类 号：R512.6[医药卫生—内科学]