血清miR-21、miR-148b、miR-200a、miR-200b在原发性肝癌患者中的表达及临床诊断意义

目的研究原发性肝癌(HCC)患者血清中微小RNA(miR)-21、miR-148b、miR-200a、miR-200b的表达及临床诊断意义。方法应用实时荧光定量逆转录-聚合酶链反应(qRT-PCR)检测西南医科大学附属医院收治的93例HCC患者(病例组)、48例肝脏良性病变(良性组)、48例慢性肝病患者(慢性肝病组)和50例健康体检者(对照组)血清中miR-21、miR-148b、miR-200a、miR-200b的表达。统计学分析各指标与临床病理特征之间的关系,受试者工作特征(ROC)曲线分析各指标的诊断价值。结果病例组血清miR-21与miR-200b表达显著高于良性组、慢性肝病组及对照组(均P<0.05),miR-200a与miR-148b表达显著低于良性组、慢性肝病组及对照组(均P<0.05)。HCC患者血清miR-21与miR-200b表达与病理分期、病理分级及肿瘤直径有关(均P<0.05),与性别、年龄、有无肝硬化及乙型肝炎病毒(HBV)抗原是否阳性无关(均P>0.05)。血清miR-200a与miR-148b表达与病理分期、病理分级有关(均P<0.05),与性别、年龄、肿瘤直径、有无肝硬化及HBV抗原是否阳性无关(均P>0.05)。miR-21、miR-148b、miR-200a、miR-200b及四项指标联合的ROC曲线下面积(AUC)分别为0.821、0.668、0.772、0.734、0.922。联合诊断的敏感性和特异性均高于任一单一指标。结论HCC患者血清miR-21与miR-200b表达上调,而miR-200a与miR-148b表达下调。并且其表达与病理分期、病理分级有关,联合检测血清miR-21、miR-148b、miR-200a、miR-200b有希望成为新的诊断HCC的肿瘤标志物。

Expressions of serum miR-21, miR-148b,miR-200a and miR-200b in patients with primary liver cancer and their clinical significance

Objective To study the expressions and clinical significances of microRNA(miR)-21,miR-148b,miR-200a and miR-200b in serum of patients with primary liver cancer(HCC).Methods Quantitative real-time PCR(qRT-PCR)was used to detect the expressions of miR-21,miR-148b,miR-200a and miR-200b in 93 HCC patients(HCC group),48 cases of benign liver lesions(benign group),47 patients with chronic liver disease(chronic liver disease group)and 50 healthy people(control group).The relationship between each index and clinicopathological features was statistically analyzed and the receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of each index.Results The expressions of serum miR-21 and miR-200b in HCC group were significantly higher than those of control group(P<0.05)and the expressions of miR-200a and miR-148b were significantly lower than those of control group(P<0.05).The expressions of serum miR-21 and miR-200b in HCC patients were correlated with pathological stage,pathological grade and tumor diameter(P<0.05)and were not associated with gender,age,presence or absence of cirrhosis and HBV antigen(P>0.05).The expressions of serum miR-200a and miR-148b were correlated with pathological stage and pathological grade(P<0.05),and were not related to gender,age,tumor diameter,presence or absence of cirrhosis and HBV antigen(P>0.05).The area under the ROC curve(AUC)of miR-21,miR-148b,miR-200a,miR-200b and the four indicators combined were 0.821,0.668,0.772,0.734,0.922,respectively.The sensitivity and specificity of diagnosis with combined indexes were higher than those of either single index.Conclusions The expressions of miR-21 and miR-200b are up-regulated in HCC patients,while the expressions of miR-200a and miR-148b are down-regulated.And their expressions are related to pathological stage and pathological grade.Combining detection of serum miR-21,miR-148b,miR-200a and miR-200b is promised as the new tumor marker for the diagnosis of HCC.