Plasma microRNAs as potential biomarkers for non-small-cell lung cancer.
Plasma microRNAs as potential biomarkers for non-small-cell lung cancer.
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血浆 microRNA 作为非小细胞肺癌的潜在生物标志物
DOI：
10.1038/labinvest.2010.194
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发表时间：
2011-04
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非小细胞肺癌（NSCLC）是癌症相关死亡的主要原因。开发能够诊断非小细胞肺癌的微创技术，特别是在早期阶段，可能会改善其预后。利用微阵列平台，我们先前鉴定了12种microrna (mirna)，它们在原发性肺肿瘤中的异常表达与早期非小细胞肺癌相关。在这里，我们扩展了之前的研究，研究mirna是否可以作为潜在的非小细胞肺癌血浆生物标志物。我们首先通过实时定量反转录PCR验证了28例I期NSCLC患者配对肺肿瘤组织和血浆标本中miRNAs的表达，然后评估了58例NSCLC患者和29例健康个体的血浆miRNAs的诊断价值。miRNA表达的改变在肿瘤组织中得到了重复性的证实。这些mirna在血浆中稳定存在且可可靠测量。在12个mirna中，有5个mirna在血浆和相应肿瘤组织中的表达水平具有显著一致性（均P<0.05， P<0.05）。基于四个基因（miRNA-21、-126、-210和486-5p）定义了最佳预测的logistic回归模型，在区分NSCLC患者和健康对照组方面的敏感性为86.22%，特异性为96.55%。此外，mirna组在识别I期NSCLC患者时具有73.33%的敏感性和96.55%的特异性。这些基因对肺腺癌的诊断敏感性（91.67%）高于鳞癌（82.35%）（P<0.05）。血浆中mirna表达的改变将为非小细胞肺癌提供潜在的血液生物标志物。
Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death. Developing minimally invasive techniques that can diagnose NSCLC, particularly at an early stage, may improve its outcome. Using microarray platforms, we previously identified 12 microRNAs (miRNAs) the aberrant expressions of which in primary lung tumors are associated with early-stage NSCLC. Here, we extend our previous research by investigating whether the miRNAs could be used as potential plasma biomarkers for NSCLC. We initially validated expressions of the miRNAs in paired lung tumor tissues and plasma specimens from 28 stage I NSCLC patients by real-time quantitative reverse transcription PCR, and then evaluated diagnostic value of the plasma miRNAs in a cohort of 58 NSCLC patients and 29 healthy individuals. The altered miRNA expressions were reproducibly confirmed in the tumor tissues. The miRNAs were stably present and reliably measurable in plasma. Of the 12 miRNAs, five displayed significant concordance of the expression levels in plasma and the corresponding tumor tissues (all r>0.850, all P<0.05). A logistic regression model with the best prediction was defined on the basis of the four genes (miRNA-21, -126, -210, and 486-5p), yielding 86.22% sensitivity and 96.55% specificity in distinguishing NSCLC patients from the healthy controls. Furthermore, the panel of miRNAs produced 73.33% sensitivity and 96.55% specificity in identifying stage I NSCLC patients. In addition, the genes have higher sensitivity (91.67%) in diagnosis of lung adenocarcinomas compared with squamous cell carcinomas (82.35%) (P<0.05). Altered expressions of the miRNAs in plasma would provide potential blood-based biomarkers for NSCLC.