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痰液中 miRNA 表达谱改变用于非小细胞肺癌的诊断。

Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer.

机构信息

Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.

出版信息

Lung Cancer. 2010 Feb;67(2):170-6. doi: 10.1016/j.lungcan.2009.04.004. Epub 2009 May 14.

Abstract

UNLABELLED

Analysis of molecular genetic markers in biological fluids has been proposed as a useful tool for cancer diagnosis. MicroRNAs (miRNAs) are small regulatory RNAs that are frequently dysregulated in lung cancer and have shown promise as tissue-based markers for its prognostication. The aim of this study was to determine whether aberrant miRNA expression can be used as a marker in sputum specimen for the diagnosis of non-small cell lung cancer (NSCLC).

EXPERIMENTAL DESIGN

expressions of mature miRNAs, mir-21 and mir-155, were examined by real-time reverse transcription polymerase chain reaction (RT-PCR) and normalized to that of control miRNA, U6B, in sputum of 23 patients with NSCLC and 17 cancer-free subjects. The data was compared with conventional sputum cytology for the diagnosis of lung cancer. All endogenous miRNAs were present in sputum in a remarkably stable form and sensitively and specifically detected by real-time RT-PCR. Mir-21 expression in the sputum specimens was significantly higher in cancer patients (76.32+/-9.79) than cancer-free individuals (62.24+/-3.82) (P<0.0001). Furthermore, overexpression of mir-21 showed highly discriminative receiver-operator characteristic (ROC) curve profile, clearly distinguishing cancer patients from cancer-free subjects with areas under the ROC curve at 0.902+/-0.054. Detection of mir-21 expression produced 69.66% sensitivity and 100.00% specificity in diagnosis of lung cancer, as compared with 47.82% sensitivity and 100.00% specificity by sputum cytology. The measurement of altered miRNA expression in sputum could be a useful noninvasive approach for the diagnosis of lung cancer.

摘要

未加说明

分析生物体液中的分子遗传标记已被提议作为癌症诊断的有用工具。微小 RNA(miRNA)是经常在肺癌中失调的小调节 RNA,并且已显示出作为组织标志物用于其预后的潜力。本研究的目的是确定异常 miRNA 表达是否可作为非小细胞肺癌(NSCLC)痰液标本的标志物用于诊断。

实验设计

通过实时逆转录聚合酶链反应(RT-PCR)检测 23 例 NSCLC 患者和 17 例无癌症对照者痰液中成熟 miRNA,miR-21 和 miR-155 的表达,并与对照 miRNA,U6B 进行归一化。数据与传统痰液细胞学检查进行比较以诊断肺癌。所有内源性 miRNA 以非常稳定的形式存在于痰液中,并且通过实时 RT-PCR 灵敏且特异性地检测到。癌症患者痰液标本中 mir-21 的表达明显高于无癌症个体(76.32+/-9.79)(P<0.0001)。此外,mir-21 的过表达显示出高度区分的接收者操作特征(ROC)曲线特征,通过 ROC 曲线下面积清楚地区分癌症患者与无癌症个体,曲线下面积为 0.902+/-0.054。与痰液细胞学检查的 47.82%敏感性和 100.00%特异性相比,检测 mir-21 表达在肺癌诊断中产生了 69.66%的敏感性和 100.00%的特异性。改变的 miRNA 在痰液中的表达的测量可能是诊断肺癌的有用的非侵入性方法。

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