Identification of Circulating miR-762 as a Novel Diagnostic and Prognostic Biomarker for Non-Small Cell Lung Cancer.

Identification of Circulating miR-762 as a Novel Diagnostic and Prognostic Biomarker for Non-Small Cell Lung Cancer.
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将循环miR-​​762鉴定为非小细胞肺癌的新型诊断和预后生物标志物。

DOI:
10.1177/1533033820964222
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发表时间:
2020-01
影响因子:
2.8
通讯作者:
Lu J
Lu J
中科院分区:
医学4区
文献类型:
--
作者:
Chen L;Li Y;Lu J

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已证实microRNAs(MiRNAs)在非小细胞肺癌(NSCLC)的发生发展中起重要作用,循环中的miRNAs是临床治疗NSCLC的重要生物标志物来源。本研究的目的是确定血清miR-762作为非小细胞肺癌诊断和预后生物标志物的价值。我们用实时定量聚合酶链式反应(qRT-PCR)检测了148例非小细胞肺癌患者和60例健康人外周血中miR-762的表达。并探讨miR-762下调对NSCLC细胞增殖能力的影响。与健康人相比,非小细胞肺癌患者血清miR-762水平显著升高。受试者工作特征(ROC)曲线分析显示,循环MIR762、癌胚抗原(CEA)、CYFRA21-1以及这3种生物标志物的组合产生的曲线下面积(AUC值)分别为0.874、0.826、0.41和0.969。有趣的是,循环中的MIR-762以0.920的AUC值从健康对照组中识别出临床I期的非小细胞肺癌患者。此外,血清miR-762的表达与临床分期、淋巴结转移、组织学分级和吉非替尼耐药显著相关。生存分析显示,高血清miR-762组NSCLC患者总体生存率和无复发生存率均低于低血清miR-762组。多因素COX比例风险回归分析显示,高循环miR-762是一个独立的预后不良因素。在体外,miR-762的下调显著抑制了NSCLC细胞的增殖能力,对miR-762潜在下游靶点的生物信息学分析发现了许多重要的癌症相关途径。结论:血清miR-762可作为非小细胞肺癌诊断和预后的生物标志物。
MicroRNAs (miRNAs) have been demonstrated to play critical roles in tumorigenesis of non-small cell lung cancer (NSCLC), and circulating miRNAs are a valuable source of biomarkers for the clinical management of NSCLC. The aim of this study was to determine the value of serum miR-762 as a diagnostic and prognostic biomarker for NSCLC. We examined circulating miR-762 expression in 148 NSCLC patients and 60 healthy individuals using the quantitative real-time polymerase chain reaction (qRT-PCR). The effect of miR-762 downregulation on the proliferative capacity of NSCLC cells were also explored. The serum miR-762 levels were significantly upregulated in NSCLC patients compared to the healthy individuals. Receiver operating characteristics (ROC) curve analysis revealed that circulating miR-762, carcinoembryonic antigen (CEA), CYFRA21-1 and a combination of these 3 biomarkers yield the areas under the curve (AUC) of 0.874, 0.826, 0.41 and 0.969, respectively. Interestingly, circulating miR-762 identified the NSCLC patients at the clinical stage I from healthy controls with an AUC value of 0.920. In addition, serum miR-762 expression was significantly correlated with clinical stage, lymph node metastasis, histological grade and gefitinib-resistance. The survival analysis showed that NSCLC patients in the high serum miR-762 group suffered worse overall survival and relapse-free survival than those in the low serum miR-762 group. The multivariate Cox proportional hazards regression analysis revealed high circulating miR-762 was an independent unfavorable prognostic factor. Downregulation of miR-762 significantly suppressed the proliferative capacity of NSCLC cells in vitro, and bioinformatic analysis of the potential downstream targets of miR-762 identified many important cancer-associated pathways. In conclusion, serum miR-762 might serve as a promising diagnostic and prognostic biomarker for the NSCLC.
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