Identification of recurrence-related serum microRNAs in hepatocellular carcinoma following hepatectomy.
Identification of recurrence-related serum microRNAs in hepatocellular carcinoma following hepatectomy.
复制标题
肝切除术后肝细胞癌复发相关血清 microRNA 的鉴定。
DOI：
10.1080/15384047.2015.1071730
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发表时间：
2015
影响因子：
3.6
通讯作者：
Xu N
中科院分区：
文献类型：
--
作者：
Wang L;Liu M;Zhu H;Rong W;Wu F;An S;Liu F;Feng L;Wu J;Xu N
肝细胞癌（Hepatocellular carcinoma，HCC）是最致命的肿瘤之一。肝癌的复发率高，预后差。本研究采用TaqMan实时荧光定量PCR microRNA芯片技术，对10例肿瘤组织标本（复发组5例，未复发组5例）及配对血清标本进行差异表达的miRNA检测。在20例肝癌组织和116例肝癌患者术前血清中进一步检测4种差异表达的miRNAs（miR-486- 5 p、miR-422 a、miR-125 b和miR-139- 5 p）。单因素分析显示，miR-486- 5 p、miR-422 a和miR-125 b与患者的无复发生存期（RFS）显著相关。多变量分析表明，miR-486- 5 p、AFP和微血管浸润（MVI）是该队列中与RFS相关的独立预后因素（分别为p = 0.000、0.043、0.000）。此外，miR-486- 5 p和miR-422 a在肿瘤组织和配对血清中的表达水平呈正相关。miR-486- 5 p预测肝癌术后1年内复发的准确率为76.79%（特异性65.38%，敏感性81.58%），与AFP和MVI联合建立的分类器的准确率（75.98%，特异性63.13%，敏感性85.90%）相当。AFP、MVI和miR-486- 5 p联合检测的ROC曲线面积为88.02%（特异性69.20%，敏感性92.10%）。我们的研究是第一个确定血清miR-486- 5 p可用于对肝切除术前复发风险较高的患者进行分层，并可能为他们提供更有效的监测策略。
Hepatocellular carcinoma (HCC) is one of the most deadly tumors. Prognosis of patients with HCC is generally poor due to the high recurrence rate. In the present study, TaqMan Real-time PCR microRNA Array was used to identify differentially expressed miRNAs from 10 tumor tissue samples (5 from recurrence group vs. 5 from non-recurrence group) and the matched serum samples. Four differentially expressed miRNAs (miR-486–5p, miR-422a, miR-125b and miR-139–5p) were further quantified in 20 tumor tissues and 116 HCC patients' serum before they received hepatectomy. Univariate analysis revealed that miR-486–5p, miR-422a and miR-125b were significantly associated with patients' relapse free survival (RFS). Multivariate analysis demonstrated that miR-486–5p, AFP and microvascular invasion (MVI) were the independent prognostic factors associated with RFS in this cohort (p = 0.000, 0.043, 0.000, respectively). Besides, the expression levels of miR-486–5p were positively correlated in tumor tissues and the paired serum samples, so was miR-422a. The probability of the prognostic accuracy of miR-486–5p in predicting postoperative recurrence of HCC within the first year was 76.79% (65.38% specificity and 81.58% sensitivity), which was almost equal to the classifier established by combination of AFP and MVI (75.98% probability, 63.13% specificity and 85.90% sensitivity). Furthermore, the combination of AFP, MVI and miR-486–5p yielded a ROC curve area of 88.02% (69.20% specificity and 92.10% sensitivity). Our study was the first to identify that serum miR-486–5p could be used to stratify the patients with higher recurrence risk before hepatic resection and potentially guide more effective surveillance strategies for them.