血清miR-148a检测作为肝癌标志物的临床价值研究

目的:探讨血清miR-148a作为肝细胞肝癌(hepatocellular carcinoma,HCC)标志物的临床应用价值?方法:实时荧光定量PCR法(quantitative real time-polymerase chain reaction,qRT-PCR)检测HCC患者血清miR-148a水平,并与良性肝病组以及健康对照组进行比较分析?结果:HCC患者血清miR-148a水平明显低于良性肝病组及健康体检组 (P < 0.001)?ROC曲线(receiver operating characteristic curve)结果显示HCC组 vs. 良性肝病组的曲线下面积(area under the curve,AUC)为0.666,95%置信区间(Confidence interval,CI)为0.581~0.744,诊断灵敏度为67.7%,特异性为59.2%(P < 0.001);HCC组 vs. 健康对照组的AUC为0.746,95%CI为0.663~0.818,诊断灵敏度为43.6%,特异性为96.1%(P < 0.001)?血清miR-148a与HCC患者肿瘤大小(P=0.011)及TNM分期(P < 0.001)有关,而与其他临床参数无明显相关性(P > 0.05)?HCC患者术后血清miR-148a水平与术前相比明显升高(P=0.023);而术后出现复发或转移的HCC患者其血清miR-148a水平明显下降,并且低于术前水平(P < 0.05)?生存曲线分析显示血清miR-148a低表达的HCC患者其总生存率明显低于血清miR-148a高表达的HCC患者(P < 0.001),Cox回归分析进一步显示血清miR-148a可作为HCC预后评估的一个独立决定因子?结论:HCC患者血清miR-148a明显降低,并与HCC病情?恶性进展及预后相关,可作为HCC诊断与鉴别诊断?病情评估?疗效观察及预后判断的指标?

Clinical value of serum miR-148a as a potential biomarker for hepatocellular carcinoma

Objective:To explore the clinical value of serum miR-148a as a potential biomarker for hepatocellular carcinoma(HCC). Methods:Quantitative real-time polymerase chain reaction (qRT-PCR)was used to inrestigate the levels of serum miR-148a in HCC patients,the patients with benign liver diseases and healthy volunteers were used as control groups. Results:Serum levels of miR-148a were significantly decreased in HCC cases than those in benign and healthy controls,P < 0.001. Receiver operating characteristic curve(ROC)showed that the area under the curve(AUC)in HCC group vs. benign group was 0.666,95% Confidence interval(CI),0.581-0.744;the diagnostic sensitivity was 67.7% and specificity was 59.2%,P < 0.001. The AUC in HCC group vs. healthy group was 0.746,95%CI,0.663~0.818;the diagnostic sensitivity was 43.6% and specificity was 96.1%,P < 0.001. In addition,serum miR-148a was significantly associated with tumor size (P=0.011) and TNM stage (P < 0.001),whereas,no significant correlation of serum miR-148a with other clinical parameters,P > 0.05. The level of serum miR-148a in postoperative HCC patients was significantly higher than that of preoperation,P=0.023. However,the level of serum miR-148a in postoperative patients with recurrence or metastasis was significantly decreased,and even lower than that of preoperative group,P < 0.05. Kaplan-Meier analysis demonstrated that the decreased serum miR-148a was closely correlated with shorten overall survival of HCC patients,P < 0.001. Besides,Cox regression model further indicated that serum miR-148a was an independent prognosis marker for HCC patients. Conclusion:The down-regulated serum miR-148 was related to disease condition,malignant progression and prognosis of HCC patients. Moreover,serum miR-148 might act as a potential marker for diagnosis and differential diagnosis,evaluation of disease,observation of curative effect and judgment of prognosis for HCC.