Tumor-Derived Exosomal miRNAs as Diagnostic Biomarkers in Non-Small Cell Lung Cancer.

Tumor-Derived Exosomal miRNAs as Diagnostic Biomarkers in Non-Small Cell Lung Cancer.
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肿瘤衍生的外泌体 miRNA 作为非小细胞肺癌的诊断生物标志物。

DOI:
10.3389/fonc.2020.560025
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发表时间:
2020
影响因子:
4.7
通讯作者:
Song X
Song X
中科院分区:
医学3区
文献类型:
--
作者:
Zhang Z;Tang Y;Song X;Xie L;Zhao S;Song X

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延迟诊断是提高非小细胞肺癌(NSCLC)预后的主要障碍。迫切需要新的诊断非小细胞肺癌的生物标志物。本研究旨在确定在非小细胞肺癌患者中具有诊断和预后潜力的特异性外体miRNAs。对330例非小细胞肺癌患者和312例健康献血员血清经超速离心法提取的外切体进行了透射电子显微镜、qNano和Western blotts分析。用miRNA微阵列分析外体miRNAs,并用定量聚合酶链式反应(QPCR)进行验证。通过受试者工作特性(ROC)分析确定诊断的准确性。通过miRNA芯片筛选出差异表达的22个miRNAs,其中外体miR-5684和miR-125b-5p在NSCLC患者中较正常对照显著下调,对(早期)NSCLC具有良好的诊断效率。重要的是,外体miR-125b-5p与转移(P<0.0001)、化疗疗效(P=0.007)和生存期(P=0.008)有关。外体miR-5684和miR-125b-5p在NSCLC患者中表达显著下调,有望成为NSCLC的诊断和预后生物标志物。
Delayed diagnosis is the main obstacle to improve prognosis of non-small cell lung cancer (NSCLC). Novel biomarkers for the diagnosis of NSCLC are urgently needed. This study aimed to identify the specific exosomal miRNAs with diagnostic and prognostic potential in NSCLC patients. Transmission electron microscopy (TEM), qNano and western blots were used to characterize the exosomes isolated from the serum of NSCLC patients (n=330) and healthy donors (n=312) by ultracentrifugation. Exosomal miRNAs were profiled by miRNA microarrays and verified by quantitative PCR (qPCR). The diagnostic accuracy was determined by receiver operating characteristic (ROC) analysis. A total of differential 22 miRNAs were screened out based on P < 0.05 and fold difference>2.0 by miRNA microarrays, among which, exosomal miR-5684 and miR-125b-5p were significantly down-regulated in NSCLC patients compared to healthy donors, processing favorable diagnostic efficiency for (early) NSCLC. Importantly, the exosomal miR-125b-5p were associated with metastasis (P < 0.0001), chemotherapeutic effect (P=0.007) and survival (P=0.008). Exosomal miR-5684 and miR-125b-5p levels are significantly down-regulated in NSCLC patients, and serve as the promising diagnostic and prognostic biomarkers for NSCLC.
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