中国普外基础与临床杂志

中国普外基础与临床杂志

miR-483-5p 在肝细胞肝癌患者血清中的表达及临床意义

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目的 检测肝细胞肝癌(简称肝癌)患者血清中 miR-483-5p 表达并探讨其对肝癌的诊断价值。 方法 收集 2010 年 1 月至 2012 年 1 月期间兰州大学第一医院收治的 112 例肝癌患者术前 1 d 及术后 1 个月以及 85 例慢性乙型病毒性肝炎患者(简称慢性乙肝)和 56 例健康对照人群的清晨空腹血清样本。利用实时定量荧光 PCR 法检测血清中 miR-483-5p 和 miR-500a 表达水平,应用操作者工作特征(ROC)曲线分析血清中 miR-483-5p 和 miR-500a 表达水平用于肝癌的诊断价值。 结果 肝癌患者血清中 miR-483-5p 和 miR-500a 表达水平均明显高于慢性乙肝患者和健康对照人群(均 P<0.000 1),但是其在慢性乙肝患者和健康对照人群间比较差异均无统计学意义(均P>0.05)。肝癌患者术后 1 个月时血清中 miR-483-5p 表达水平较术前明显下降(P<0.000 1)。miR-483-5p、miR-500a、甲胎蛋白(AFP)及 miR-483-5p 与 AFP 联合诊断肝癌的 ROC 曲线下面积(AUC)分别是 0.74、0.66、0.81 及 0.92,当 miR-483-5p 临界值为 2.84 时的诊断敏感度与特异度分别为 74% 和 66%,当 miR-500a 的临界值为 1.83 时的诊断灵敏度和特异度分别是 74% 和 51%,当 AFP 的临界值为 20 时的诊断敏感度与特异度分别为 78% 和 70%,当 miR-483-5p 与 AFP 联合使用的临界值为 3.78 时的诊断灵敏度和特异度分别为 81% 和 83%。miR-483-5p 表达诊断 AFP 阳性(AFP>20 μg/L)和 AFP 阴性(0~20 μg/L)肝癌患者的AUC 值分别为 0.78 和 0.83。 结论 miR-483-5p 在肝癌患者的血清中呈高表达,其诊断肝癌有一定准确性,与 AFP 联合可以提高其诊断价值,并且其对 AFP 阴性肝癌患者的诊断具有重要的补充作用。

Objective To detect expression of miR-483-5p in surem of patients with hepatocellular carcinoma (HCC) and investigate it’s clinical significance for diagnosis of HCC. Methods The rerum samples of 112 patients with HCC (HCC group), 85 patients with chronic viral hepatitis B (CHB group), and 56 healthy people for physical examination (healthy control group) were collected from January 2010 to January 2012 in the First Hospital of Lanzhou University. According to the results of preliminary chip detection of miRCURY LNATM miRNA, the real-time fluorescent quantitative PCR was adopted to quantitate the serum levels of miR-483-5p and miR-500a in every group. And receiver operating characteristic (ROC) curve was utilized to analyze the diagnostic values of serum miR-483-5p and miR-500a for HCC. Results The serum levels of miR-483-5p and miR-500a in the HCC group were significantly higher than those of the CHB and healthy controls groups (both P<0.000 1), which had no significant difference between the CHB group and the healthy control group (P>0.05). The serum level of miR-483-5p of HCC patients decreased markedly postoperative 30 d (P<0.000 1). The area under the ROC curve (AUC) of miR-483-5p, miR-500a, alpha-fetoprotein (AFP), and miR-483-5p in combination with AFP for diagnosis of HCC was 0.74 (cutoff value=2.824, sensitivity=74%, and specificity=66%), 0.66 (cutoff value=1.83, sensitivity=74%, and specificity=51%), 0.81 (cutoff value=20, sensitivity=78%, and specificity=70%), and 0.92 (cutoff value=3.78, sensitivity=81%, and specificity=83%), respectively. The AUC values of miR-483-5p in the diagnosis of AFP positive (AFP>20 μg/L) and AFP negative (0–20 μg/L) HCC patients were 0.78 and 0.83, respectively. Conclusion Serum miR-483-5p highly expresses in HCC, which has a certain accuracy in diagnosis of HCC, it combined with AFP could further increase its diagnostic value. Serum miR-483-5p might complement AFP in detecting HCC.

关键词: miRNA; 标志物; 肝细胞肝癌; miR-483-5p; 甲胎蛋白

Key words: miRNA; marker; hepatocellular carcinoma; miR-483-5p; alpha-fetoprotein

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