Objective Explore the relative expression of miR-122-5p and miR-486-5p in the serum of Hepatocellular carcinoma ( HCC) patients and its clinical value .Methods Case-control study was used in this research.From June of 2016 to March of 2017,60 HCC patients who were hospitalized in Guangzhou General Hospital were selected as HCC group .It also selected 20 hepatitis patients ( hepatitis group ) , 20 cirrhosis patients ( cirrhosis group ) , 20 breast cancer patients ( breast cancer group ) , 20 gastric cancer patients(gastric cancer group)and 20 healthy controls (normal control group) for comparison.The relative expression of miR-122-5p and miR-486-5p was detected by real-time fluorescent quantitative PCR.The specificity and sensitivity of miRNAs for the diagnosis of HCC were analyzed by receiver operating characteristic ( ROC) , and the results were compared with the tumor marker AFP .The effect of miRNA on the diagnosis of hepatocellular carcinoma was evaluated by the area under the ROC curve , which was used to detect the diagnostic efficiency of liver cancer .SPSS22.0 statistical software was used for statistical analysis . The rank sum test was applied in the group comparison .Results Serum levels of miR-122-5p in HCC group, hepatitis group, cirrhosis group, breast cancer group, gastric cancer group and control group were 0.14(0.05-0.51),0.45(0.32-0.58),0.53(0.34-0.67),0.14(0.07-0.28),0.29(0.13-0.36) and 0.73 (0.63-0.95),respectively, and the miR-486-5p were 0.50(0.23-0.77),0.62(0.48-0.82),0.65(0.54-0.85),0.23(0.08-0.40),0.29(0.15-0.45)and 0.76(0.69-1.23).The serum levels of miR-122-5p in hepatitis group , cirrhosis group , HCC group were significantly lower in healthy control group , significance was found (U was 315.37,393.46,429.08, all P<0.01), and the serum levels of miR-486-5p in hepatitis group, cirrhosis group, HCC group were lower in healthy control group , significance was found ( U was 103.67,156.18,207.35, all P<0.05).When using one serum marker to diagnosis HCC , AFP had the highest sensitivity ( 73.7％) and miR-122-5p had the highest specificity ( 95％) .While combined two serum markers, AFP +miR-122-5p had the highest sensitivity and specificity (93％),and miR-122-5p +miR-486-5p had the highest specificity (70％), compared AFP +miR-122-5p to AFP, AUC difference was statistically significant(Z=3.02,P<0.01), while there was no significant difference in AUC with AFP +miR-486-5p, miR-122-5p +miR-486-5p to AFP(Z=1.57,1.39,all P>0.05).The sensitivity and specificity of the three markers were 96.5％and 55％respectively , and the area under the ROC curve was 0.891 (95％CI:0.818-0.964).The combination miR-122-5p, miR-486-5p and AFP were higher than the single test, compared with AFP, miR-122-5p, miR-486-5p, the AUC differences was statistically significant (Z=3.26, 3.72, 4.25, all P<0.01).Conclusion Serum miR-122-5p and miR-486-5p could be used as biological markers for the diagnosis of HCC .%目的 探讨肝癌患者血清miR-122-5p和miR-486-5p的表达水平,及两指标单独或与甲胎蛋白(AFP)联合诊断肝癌的临床应用价值.方法 采用病例对照研究.选择2016年6月至2017年3月在广州军区广州总医院住院的60例肝癌患者(HCC组),20例肝炎患者(肝炎组),20例肝硬化患者(肝硬化组),20例乳腺癌患者(乳腺癌组),20例胃癌患者(胃癌组)及20名健康体检人员(正常对照组),提取总RNA,采用实时荧光定量PCR技术,检测血清中miR-122-5p和miR-486-5p的相对表达量.用受试者工作特征曲线(receiver operating characteristic,ROC)分析miRNA对肝癌诊断的特异度和灵敏度,并与肿瘤标志物AFP的测定结果进行比较.根据ROC曲线下面积判断诊断效能,评估其在肝癌诊断中的应用价值.各组间比较采用非参数秩和检验进行分析.结果 肝癌组、肝炎组、肝硬化组、乳腺癌组、胃癌组及健康对照组中血清miR-122-5p的相对表达量分别是0.14(0.05～0.51)、0.45(0.32～0.58)、0.53(0.34～0.67)、0.14(0.07～0.28)、0.29(0.13～0.36)和0.73(0.63～0.95),血清miR-486-5p的相对表达量分别是0.50(0.23～0.77)、0.62(0.48～0.82)、0.65(0.54～0.85)、0.23(0.08～0.40)、0.29(0.15～0.45)和0.76(0.69～1.23).肝炎组、肝硬化组、肝癌组中血清miR-122-5p的相对表达量较健康对照组低,差异均有统计学意义(U值分别为315.37,393.46,429.08,P均<0.01),肝炎组、肝硬化组、肝癌组中血清miR-486-5p的相对表达量较健康对照组较低,差异均有统计学意义(U值分别为103.67,156.18,207.35,P均<0.05).单项检测HCC时,AFP的敏感度最高(73.7％),miR-122-5p的特异度最高(95％).双项检测HCC时,AFP+miR-122-5p的敏感度最高(93％),miR-122-5p和miR-486-5p的特异度最高(70％),AFP+miR-122-5p的联合检测与单项AFP相比,AUC差异有统计学意义(Z=3.02,P<0.01),而AFP+miR-486-5p及miR-122-5p+miR-486-5p较AFP单项检测AUC差异无统计学意义(Z=1.57,1.39,P均>0.05).三项联合检测时,敏感度和特异度分别为96.5％和55％,ROC曲线下面积AUC为0.891(95％CI:0.818～0.964),三项联合检测时高于单独检测,且与AFP、miR-122-5p及miR-486-5p相比,AUC差异均有统计学意义(Z=3.26,3.72,4.25,P均<0.01).结论 血清miR-122-5p和miR-486-5p有可能成为肝癌辅助诊断的血清学标志物.
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