Serum exosomal miR-125b is a novel prognostic marker for hepatocellular carcinoma.
Serum exosomal miR-125b is a novel prognostic marker for hepatocellular carcinoma.
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血清外泌体 miR-125b 是肝细胞癌的新型预后标志物
DOI：
10.2147/ott.s140062
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发表时间：
2017
影响因子：
4
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Liu W;Hu J;Zhou K;Chen F;Wang Z;Liao B;Dai Z;Cao Y;Fan J;Zhou J
肝细胞癌（HCC）是全球第六大常见癌症，死亡率较高。循环微小RNA已被证明是许多肿瘤的一种新型无创生物标志物。本研究旨在探讨循环miR - 125b作为肝细胞癌预后标志物的潜力。从两个独立队列收集的血清样本中提取外泌体：队列1：肝细胞癌（n = 30），慢性乙型肝炎（CHB，n = 30），肝硬化（LC，n = 30）；队列2：肝细胞癌（n = 128）。我们发现，与慢性乙型肝炎、肝硬化和肝细胞癌患者的血清相比，外泌体中的miR - 125b水平显著升高（分别P < 0.01）。然而，肝细胞癌患者外泌体和血清中的miR - 125b水平低于慢性乙型肝炎患者（外泌体中P < 0.01，血清中P = 0.06）和肝硬化患者（均P < 0.01）。此外，外泌体中的miR - 125b水平与肿瘤数量（P = 0.02）、包膜情况（P < 0.01）和TNM分期（P < 0.01）相关。Kaplan - Meier分析表明，外泌体miR - 125b水平较低的肝细胞癌患者复发时间（TTR）缩短（P < 0.01），总生存期（OS）缩短（P < 0.01）。此外，多变量分析显示，外泌体中的miR - 125b水平，而非血清中的水平，是复发时间（P < 0.001）和总生存期（P = 0.011）的独立预测因素。外泌体miR - 125b水平预测肝细胞癌患者复发和生存的ROC曲线下面积分别为0.739（敏感性83.0%，特异性67.9%）和0.702（敏感性82.5%，特异性53.4%）。总之，外泌体miR - 125b可作为肝细胞癌一种有前景的预后标志物。
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide with high mortality. Circulating miRNA has been demonstrated as a novel noninvasive biomarker for many tumors. This study aimed to investigate the potential of circulating miR-125b as a prognostic marker of HCC. Exosomes were extracted from serum samples collected from two independent cohorts: cohort 1: HCC (n=30), chronic hepatitis B (CHB, n=30), liver cirrhosis (LC, n=30); cohort 2: HCC (n=128). We found that miR-125b levels were remarkably increased in exosomes compared to those in serum from patients with CHB, LC, and HCC (P<0.01, respectively). However, miR-125b levels in exosomes and the serum from HCC patients were inferior to that of CHB (P<0.01 and P=0.06) and LC patients (P<0.01 for all). Additionally, miR-125b levels in exosomes were associated with tumor number (P=0.02), encapsulation (P<0.01), and TNM stage (P<0.01). Kaplan–Meier analysis indicated that HCC patients with lower exosomal miR-125b levels showed reduced time to recurrence (TTR) (P<0.01) and overall survival (OS) (P<0.01). Furthermore, multivariate analysis revealed that miR-125b level in exosomes, but not in serum, was an independent predictive factor for TTR (P<0.001) and OS (P=0.011). Exosomal miR-125b levels predicted the recurrence and survival of HCC patients with an area under the ROC curve of 0.739 (83.0% sensitivity and 67.9% specificity) and 0.702 (82.5% sensitivity and 53.4% specificity). In conclusion, exosomal miR-125b could serve as a promising prognostic marker for HCC.