肝癌组织miR-148a表达变化及其与患者临床病理参数和术后早期复发的关系

Expression changes of miR-148a in hepatic carcinoma tissues and its relationships with clinicopathological parameters and early post-operative recurrence

目的观察原发性肝癌(HCC)组织微小RNA-148a(miR-148a)mRNA表达变化,并分析其与患者临床病理参数和术后早期复发的关系。方法选择HCC组织及其配对的癌旁正常组织各142例份,采用qRT-PCR法检测miR-148a mRNA表达。分析HCC组织miR-148a mRNA表达与患者临床病理参数及术后早期复发的关系。结果 HCC组织miR-148a mRNA相对表达量明显低于癌旁正常组织(P<0.05)。以142例HCC患者miR-148a mRNA相对表达量的均数为截断值,将患者分为miR-148a mRNA高表达者65例和miR-148a mRNA低表达者77例。miR-148a mRNA表达与肿瘤大小、微血管侵犯及TNM分期有关(P均<0.05),而与年龄、性别、肝硬化、血清AFP水平、HBV感染、组织分化程度及肿瘤数目无关(P均>0.05)。142例HCC患者中,早期复发88例、未复发54例。早期复发者miR-148a mRNA相对表达量明显低于未复发者(P<0.05)。88例早期复发者中,miR-148a mRNA低表达者55例、miR-148a mRNA高表达者33例,miR-148a mRNA低表达者早期复发率明显高于miR-148a mRNA高表达者(P<0.05)。采用受试者工作特征(ROC)曲线评价miR-148a mRNA预测HCC术后早期复发的价值,结果显示,miR-148a mRNA预测HCC术后早期复发的ROC曲线下面积为0.710(95%CI:0.660~0.769,P<0.01),其cut off值为0.31,此时miR-148a mRNA预测HCC术后早期复发的敏感性、特异性分别77.1%、71.8%。结论 HCC组织中miR-148a mRNA低表达,其表达变化与肿瘤进展有关。miR-148a mRNA可作为HCC患者术后早期复发的预测因子之一。

To observe the expression changes of microRNA-148a（ miR-148a） in the primary hepatic carcinoma（ HCC） tissues,and further to analyze its relationships with the clinicopathological parameters of patients and their early post-operative recurrence. Methods Quantitative RT-PCR（ qRT-PCR） were used to detect the relative expression of miR-148 a in 142 cases of HCC tissues and 142 cases of paired adjacent normal tissues. The relationships between miR-148 a expression and the clinicopathological parameters as well as early post-operative recurrence in HCC patients were analyzed. Results The relative expression of miR-148 a was significantly lower in HCC tissues than in the adjacent normal tissues（ P〈0. 05）. The mean of the relative expression of miR-148 a in HCC tissues from 142 patients was set as cut-off value,thereafter,patients were categorized into the high-expression group（ n = 65） and low-expression group（ n = 77）. The expression of miR-148 a was significantly associated with tumor size,microvascular invasion,and TNM stages（ P〈0. 05）,while was not statistically associated with age,gender,cirrhosis,serum level of AFP,HBV infection,histological differentiation,or tumor numbers（ P〉0. 05）. In the 142 HCC patients,88 of them suffered from early post-operative recurrence,while the other 54 patients did not. The expression of miR-148 a was significantly lower in patients with early post-operative recurrence than that of those without recurrence（ P〈0. 05）. In the 88 patients with early post-operative recurrence,there were 55 cases of patients with low expression of miR-148 a and 33 patients with high expression of miR-148 a. The early recurrence rate was significantly higher in patients with low expression of miR-148 a than that of those with high expression of miR-148a（ P〈0. 05）. Receiver operating characteristic（ ROC） curve was used to evaluate the predictive value of miR-148 a in early post-operative recurrence. Consequently,area under the curve was 0. 710（ 95% CI： 0. 660-0. 769,P〈 0. 01）,and the cut-off value of relative mRNA expression of miR-148 a was 0. 31. Therefore,the sensitivity and specificity of miR-148 a expression in predicting early post-operative recurrence of HCC was 77. 1% and 71. 8%,respectively.Conclusion The miR-148 a is low expressed in HCC tissues,and the expression change is associated with tumor progression. Moreover,miR-148 a can be taken as an effective predictive indicator for early post-operative recurrence of HCC.