甲胎蛋白阴性肝癌射频消融治疗前血清中转移相关 miRNA 的临床价值

The clinical significance of the expression level of metastasis-related microRNA in the serum in AFPnegative hepatocellular carcinoma patients before radiofrequency ablation

目的血清miRNA可作为肿瘤诊断、疗效及预后判断的潜在标记物。本研究旨在探索转移相关miRNA(miR-18b)在经射频消融术(RFA)治疗的AFP阴性(≤20 ng/ml)肝癌患者血清中的表达及其临床意义。方法自2007年1月—2011年1月,接受RFA治疗的AFP阴性肝癌患者131例纳入本研究,收集RFA术前血清标本并选择43例正常人血清作对照组。采用实时定量PCR方法检测血清中miR-18b的表达水平,并分析其表达水平高低与临床病理、术后复发、总生存率及无复发生存率之间的关系。结果在肝癌患者血清中miR-18b表达水平显著高于正常人(2.93±1.33对1.08±0.45,P<0.01),且高表达的miR-18b与肝硬化(P=0.035)、肿瘤直径(P<0.01)及肿瘤分化程度(P=0.020)密切相关。随访期间,79例(60.3%)患者出现复发,复发患者血清中miR-18b水平较无复发患者显著升高(3.26±1.28对2.42±0.86,P<0.01)。与miR-18b低表达的患者相比,高表达患者RFA术后复发的发生率显著较高(72.3%对48.5%,P=0.005),尤其是肝内远处转移率。Kaplan-Meier生存分析显示血清miR-18b高表达的患者总生存率及无复发生存率均显著短于低表达者。结论血清miR-18b在AFP阴性肝癌患者血清中显著升高,或可作为监测RFA术后复发及预后的理想标记物。

Objective Serum miRNA has been regarded as a potential biomarker for diagnosis, therapeutic evaluation and prognostic prediction in cancer patients. This study aims to explore the clinical significance of the expression level of metastasis- related microRNA （miR- 18b） in the serum in AFP- negative （≤ 20 ng/ml） hepatocellular carcinoma（HCC） patients receiving radiofrequency ablation （RFA）. Methods A total of 131 HCC patients with negative serum AFP, who were encountered during the period from January 2007 to January 2011 at authors’ hospital, were enrolled in this study. Radiofrequency ablation （RFA） of the lesions was carried out in all patients. Serum samples were collected before RFA. Forty - three healthy individuals were selected for control. The expression level of serum miR - 18b was deternmined by using quantitative real- time PCR method in all the patients and the healthy individuals. The correlations of the expression level of serum miR - 18b with clinico - pathological factors, postoperative recurrence, overall cirrhosis （P = 0.035）, tumor diameter （P 〈 0.01） and tumor differentiation （P = 0.020）. During the follow-up period, 79 patients （60.3%） developed recurrent tumors, and the expression level of serum miR- 18b in them was dramatically higher than that in the patients showing no recurrence （3.26 ± 1.28 vs. 2.42 ± 0.86, P 〈0.01）. The incidence of recurrence after RFA, especially distant intrahepatic metastasis, in patients with higher expression level of serum miR- 18b was strikingly higher than that in patients with lower expression level of serum miR- 18b （72.3% vs. 48.5%, P = 0.005）. Kaplan- Meier survival analysis indicated that both overall survival rate and recurrence- free survival rate of patients with higher expression level of serum miR-18b were significantly lower than those of patients with lower expression level of serum miR- 18b. Conclusion The expression level of serum miR - 18b is significantly elevated in AFP - negative HCC patients. The expression level of serum miR- 18b might be used as an ideal biomarker for monitoring tumor recurrence as well as for predicting prognosis after RFA.