Serum miR-182 and miR-331-3p as diagnostic and prognostic markers in patients with hepatocellular carcinoma
Serum miR-182 and miR-331-3p as diagnostic and prognostic markers in patients with hepatocellular carcinoma
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DOI：
10.1007/s13277-015-3430-2
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发表时间：
2015-09-01
期刊：
影响因子：
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通讯作者：
Wang, Feng
中科院分区：
文献类型：
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作者：
Chen, Lin;Chu, Feihu;Wang, Feng
以前的研究已经发现了一些在肝细胞癌组织中异常表达的微RNA(MiRNAs)。然而，它们在血清中的诊断和预后价值还没有得到充分的评估。本研究采用实时荧光定量聚合酶链式反应技术检测了103例肝细胞癌患者、95例良性肝病患者和40例健康人血清中miR-182、miR-331-3p、miR-197、miR-492和miR-581的水平。结果表明，与良性肝病和健康对照组相比，肝癌患者血清MIR-182和MIR-331-3p水平显著升高(P均<0.001)。MIR-182和MIR-331-3P的受试者-工作特征曲线下面积分别为0.911(95%CI，0.863~0.947)和0.890(95%CI，0.838~0.930)，敏感性分别为78.6%和79.61%，特异性分别为91.58%和86.32%。联合检测血清miR-182、miR-331-3p和甲胎蛋白(AFP)可显著提高对肝脏良恶性疾病的鉴别诊断价值，尤其优于单独检测AFP，P<；0.05。血清miR-182与甲胎蛋白(P=0.001)、肿瘤大小(P=0.013)、肿瘤分期(P=0.003)呈正相关，而与血清miR-331-3p呈显著正相关(P=0.006)。Kaplan-Meier生存曲线、单因素和多因素Cox比例风险分析进一步揭示，血清miR-182和miR-331-3p与肝癌患者术后生存有关，是影响肝癌患者预后的独立因素。综上所述，我们目前的研究表明，血清miR-182和miR-331-3p在肝细胞癌中表达上调，可以为肝细胞癌的诊断和预后提供积极的价值。
Previous studies have identified a number of microRNAs (miRNAs) that were aberrantly expressed in hepatocellular carcinoma (HCC) tissues. Nevertheless, their diagnostic and prognostic value in serum has not been fully evaluated. Herein, the levels of five serum miRNAs, namely, miR-182, miR-331-3p, miR-197, miR-492, and miR-581, were detected in 103 HCC patients, 95 benign liver diseases, and 40 healthy controls using real-time PCR technique. The results showed that, compared with benign liver diseases and healthy controls, the levels of serum miR-182 and miR-331-3p were significantly increased in HCC patients, both P < 0.001. Area under the receiver-operating characteristic (ROC) curves for serum miR-182 and miR-331-3p were 0.911 (95 % CI, 0.863-0.947) and 0.890 (95 % CI, 0.838-0.930), the sensitivity were 78.6 and 79.61 %, and the specificity were 91.58 and 86.32 %, respectively. Moreover, the combination of serum miR-182, miR-331-3p, and alpha-fetoprotein (AFP) can markedly increase the differential diagnostic value of benign and malignant liver diseases, especially better than serum AFP alone, P < 0.05. Serum miR-182 was positively correlated with serum AFP (P = 0.001), tumor size (P = 0.013), and TNM classification of malignant tumors (TNM) stage (P = 0.003); however, only TNM stage was demonstrated a significant correlation with serum miR-331-3p (P = 0.006). In addition, Kaplan-Meier survival curve, together with univariate and multivariate Cox proportional hazard analyses, further disclosed that serum miR-182 and miR-331-3p were associated with postoperative survival of HCC patients, and both of them were regarded to be independent prognostic factors for patients with HCC. Taken together, our present study indicates that serum miR-182 and miR-331-3p, upregulated in HCC, can provide positive diagnostic and prognostic values for HCC.