Identification of a six-miRNA panel in serum benefiting pancreatic cancer diagnosis
Identification of a six-miRNA panel in serum benefiting pancreatic cancer diagnosis
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血清中六种 miRNA 的鉴定有利于胰腺癌的诊断
DOI：
10.1002/cam4.2145
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发表时间：
2019-06-01
期刊：
影响因子：
4
通讯作者：
Miao, Yi
中科院分区：
文献类型：
--
作者：
Zou, Xuan;Wei, Jishu;Miao, Yi
胰腺癌已经对全世界越来越多的人的健康构成了巨大的威胁。血清mirna检测具有灵敏度高、无创、易获得等特点，有望成为PC患者的一种新型筛查方法。在本研究中，我们通过qRT-PCR检测了血清中miRNA的表达水平。研究分为四个阶段：筛选、培训、测试和外部验证阶段。在筛选阶段，我们首先使用Exiqon面板选择候选mirna。然后，在接下来的训练和测试阶段，对129份PC血清样本和107份正常对照（nc）进行进一步分析，以鉴定不同表达的mirna。在外部验证阶段，使用30个PC血清样本和30个nc血清样本来确认鉴定的mirna的诊断价值。此外，我们还进一步研究了另外44例PC肿瘤组织样本及其匹配的邻近正常组织样本以及32对血清来源的外泌体样本中miRNA的表达情况。结果，我们在PC患者的血清中发现了6个显著上调的mirna: let-7b-5p、miR-192-5p、miR-19a-3p、miR-19b-3p、miR-223-3p和miR-25-3p。然后在血清中建立6 - mirna面板。在联合训练和测试阶段，该小组的受试者工作特征曲线下面积（AUC）为0.910，显示出比单个miRNA更高的诊断价值。采用Cox比例风险模型和Kaplan-Meier曲线进行预后价值预测显示，血清miR-19a-3p升高与总生存期（OS）恶化密切相关。此外，在PC组织和血清来源的外泌体样本中均观察到miR-192-5p、miR-19a-3p和miR-19b-3p的显著上调。总之，我们在血清中鉴定出6种mirna (let-7b-5p、miR-192-5p、miR-19a-3p、miR-19b-3p、miR-223-3p和miR-25-3p)，用于PC早期和无创诊断。
Pancreatic cancer (PC) has posed a great health threat to a growing number of people all over the world. Detection of serum miRNAs, being sensitive, noninvasive, and easy to obtain, has a great potential of being a novel screening method for PC patients. In this study, we investigated miRNA expression levels in serum by qRT-PCR. The study was divided into four phases: the screening, training, testing, and external validation stage. We firstly chose candidate miRNAs using Exiqon panels in the screening phase. Then, a total of 129 PC serum samples and 107 normal controls (NCs) were further analyzed in the following training and testing phases to identify differently expressed miRNAs. A cohort of 30 PC serum samples vs 30 NCs was used to confirm the diagnostic value of the identified miRNAs in the external validation phase. Moreover, miRNA expressions in additional 44 PC tumor tissue samples and the matched adjacent normal tissue samples as well as 32 pairs of serum-derived exosomes samples were also further explored. As a result, we identified six significantly upregulated miRNAs in the serum of PC: let-7b-5p, miR-192-5p, miR-19a-3p, miR-19b-3p, miR-223-3p, and miR-25-3p. A six-miRNA panel in serum was then established. The area under the receiver operating characteristic curves (AUC) for the panel was 0.910 for the combined training and testing phases, which showed higher diagnostic value than the individual miRNA. Prognostic value prediction using Cox's proportional hazards model and Kaplan-Meier curves showed that increased serum miR-19a-3p was closely related to worse overall survival (OS). In addition, significant upregulation of miR-192-5p, miR-19a-3p, and miR-19b-3p was observed in both PC tissue and serum-derived exosomes samples. In conclusion, we identified a six-miRNA (let-7b-5p, miR-192-5p, miR-19a-3p, miR-19b-3p, miR-223-3p, and miR-25-3p) panel in the serum for PC early and noninvasive diagnosis.