CAJ | 학술논문

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。
목적：혈청 miRNA 가작위종류진단、료효급예후판단적잠재표기물。본연구지재탐색전이상관 miRNA（miR-18b）재경사빈소융술（RFA）치료적 AFP 음성（≤20 ng/ml）간암환자혈청중적표체급기림상의의。방법자2007년1월-2011년1월，접수 RFA 치료적 AFP 음성간암환자131례납입본연구，수집 RFA 술전혈청표본병선택43례정상인혈청작대조조。채용실시정량 PCR 방법검측혈청중miR-18b 적표체수평，병분석기표체수평고저여림상병리、술후복발、총생존솔급무복발생존솔지간적관계。결과재간암환자혈청중 miR-18b 표체수평현저고우정상인（2．93±1．33대1．08±0．45，P <0．01），차고표체적 miR-18b 여간경화（P =0．035）、종류직경（P <0．01）급종류분화정도（P =0．020）밀절상관。수방기간，79례（60．3%）환자출현복발，복발환자혈청중 miR-18b 수평교무복발환자현저승고（3．26±1．28대2．42±0．86，P <0．01）。여 miR-18b 저표체적환자상비，고표체환자 RFA 술후복발적발생솔현저교고（72．3%대48．5%，P =0．005），우기시간내원처전이솔。 Kaplan- Meier 생존분석현시혈청 miR-18b 고표체적환자총생존솔급무복발생존솔균현저단우저표체자。결론혈청 miR-18b 재 AFP 음성간암환자혈청중현저승고，혹가작위감측 RFA 술후복발급예후적이상표기물。
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.