循环miR-106a/b表达水平在肝细胞癌的诊断及预后中的作用

The Role of miR-106a/b Expression Levels in the Diagnosis and Prognosis of Hepatocellular Carcinoma

目的评估循环miR-106a/b表达水平在肝细胞癌(HCC)诊断及预后中的作用。方法纳入108例HCC患者和54例健康志愿者(HCs),采集受试者外周血,并采用实时荧光定量PCR进行miR-106a/b表达水平的检测。对HCC患者进行随访,并记录其总体生存期(OS)。结果 HCC患者中血浆miR-106a表达水平显著高于HCs(P<0.001)。血浆miR-106b在HCC患者中表达同样升高(P<0.001)。受试者工作特征曲线显示miR-106a/b的诊断效能较好,曲线下面积分别为0.670(95%CI:0.573~0.768)和0.684(95%CI:0.593~0.776)。HCC患者中循环miR-106a表达量与乙型肝炎病毒表面抗原(HBsAg)(P=0.028)、病理分化(P=0.025)、肿瘤大小(P=0.002)、淋巴结转移(P=0.028)以及TNM分级(P=0.037)正相关;miR-106b表达量与HBsAg(P=0.003)、AFP(P=0.031)以及肿瘤大小(P=0.005)正相关。Kaplan-Meier曲线分析显示,血浆miR-106a高水平的HCC患者具有较差的OS(P=0.013)。多因素Cox回归模型分析显示,miR-106a高表达是HCC患者OS差的独立预测因素(P=0.038)。结论循环miR-106a/b表达水平可作为HCC患者的诊断标志物,且循环miR-106a高表达是HCC患者预后不良的独立预测因素。

Objective To investigate the role of microRNA-106a and microRNA-106b （miR-106a/b） in diagnosis and prognosis of hepatocellu- lar carcinoma （HCC）. Methods In this study, 108 HCC patients and 54 age- and sex-matched healthy controls were enrolled. Blood samples were collected from each participant, and total RNA was extracted from the plasma. We determined miR- 106a/b expression levels using quantita- tive reverse tt-anscription polymerase chain reaction （qRT-PCR）. Results The miR-106a/b expression levels in HCC patients were elevated compared with the healthy controls （P 〈 0.001 ）. The ROC curve analysis showed that miR-106a/b expression levels could be used to predict the risk of HCC, with AUC values of 0.670 （95% Ch 0.573-0.768） and 0.684 （95% CI： 0.593-0.776）, respectively. The miR-106a expression level in HCC patients correlated positively with hepatitis B surface antigen （HBsAg） presence （P = 0.028 ）, differentiation （P = 0.025 ）, tumor size （P = 0.002 ）, lymph node metastasis （P = 0.028 ）, and TNM stage （P = 0.037 ）. The miR-106b expression level correlated positively with HBsAg presence （ P = 0.003 ）, alpha-fetoprotein （AFP） level （P = 0.031 ）, and tumor size （ P = 0.005 ）. To further investigate the correlation of miR- 106a/b expression levels with overall survival （OS）, Kaplan-Meier curves were plotted. The results showed that HCC patients with high miR-106a expres- sion displayed shorter OS （P = 0.013）. In addition, univariate and multivariate Cox proportional hazards regression showed that miR- 106a was an independent risk factor for HCC prognosis. Conclusion Circulating miR- 106a/b expression levels could he used as diagnostic biomarkers for HCC, and a high circulating miR-106a expression level is an independent risk factor for poor prognosis of HCC patients.