Differential miRNA expressions in peripheral blood mononuclear cells for diagnosis of lung cancer.
Differential miRNA expressions in peripheral blood mononuclear cells for diagnosis of lung cancer.
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DOI：
10.1038/labinvest.2015.88
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Jiang F
中科院分区：
文献类型：
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作者：
Ma J;Lin Y;Zhan M;Mann DL;Stass SA;Jiang F
已经做出了巨大的努力来通过检测直接从肿瘤释放的循环细胞外miRNA来开发癌症生物标志物。然而，无细胞生物标志物中没有一种被接受用于早期检测非小细胞肺癌（NSCLC）。外周血单核细胞（PBMC）是免疫系统抵御恶性肿瘤的第一道防线，其功能障碍可能是肿瘤免疫原性或免疫逃避的早期事件。我们建议研究PBMCs的miRNA表达分析是否对NSCLC具有诊断价值。我们首先使用微阵列分析了16名I期NSCLC患者和16名无癌症吸烟者的PBMC，并鉴定了7种在NSCLC患者中表达水平显著改变的PBMC miRNA。在84名NSCLC患者和69名无癌症吸烟者的训练集中，从7种PBMC miRNA中开发出两种miRNA（miR-19 b-3 p和-29b-3p），在识别NSCLC中产生72.62%的灵敏度和82.61%的特异性。此外，miRNAs可以识别鳞状细胞肺癌（SCC），一种主要类型的NSCLC，80.00%的敏感性和89.86%的特异性。miRNAs的表达水平与疾病分期无关。在56名NSCLC患者和46名对照的测试集中，生物标志物的性能得到了可重复的证实。该研究首次深入分析了NSCLC患者的PBMC miRNA谱。PBMC miRNAs的检测可能为NSCLC的早期诊断提供新的方法。
Tremendous efforts have been made to develop cancer biomarkers by detecting circulating extracellular miRNAs directly released from tumors. Yet none of the cell-free biomarkers has been accepted to be used for early detection of non-small cell lung cancer (NSCLC). Peripheral blood mononucleated cells (PBMCs) act as the first line of defense against malignancy in immune system, their dysfunction may occur as an early event in cancer immunogenicity or immune evasion. We proposed to investigate if analysis of miRNA expressions of PBMCs has diagnostic value for NSCLC. We first used a microarray to analyze PBMCs of 16 stage I NSCLC patients and 16 cancer-free smokers, and identified seven PBMC miRNAs with a significantly altered expression level in NSCLC patients. In a training set of 84 NSCLC patients and 69 cancer-free smokers, a panel of two miRNAs (miRs-19b-3p and -29b-3p) were developed from the seven PBMC miRNAs, producing 72.62% sensitivity and 82.61% specificity in identifying NSCLC. Furthermore, the miRNAs could identify squamous cell lung carcinoma (SCC), a major type of NSCLC, with 80.00% sensitivity and 89.86% specificity. The expression levels of the miRNAs were independent of disease stage. In a testing set of 56 NSCLC patients and 46 controls, the performance of the biomarkers was reproducibly confirmed. The study presents the first in-depth analysis of PBMC miRNA profile of NSCLC patients. The assessment of PBMC miRNAs may provide a new diagnostic approach for the early detection of NSCLC.