Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, South Korea.
Int J Cancer. 2013 Aug 1;133(3):645-52. doi: 10.1002/ijc.28054. Epub 2013 Feb 25.
Circulating cell-free microRNAs (miRNAs) are potential cancer biomarkers. The aim of this study was to identify miRNAs that are differentially expressed between benign pleural effusion (BPE) and lung adenocarcinoma-associated malignant pleural effusion (LA-MPE). The expression level of cell-free miRNA was investigated in 107 patients with pleural effusion. Microarrays were used to screen 160 miRNAs in a discovery set comprising 20 effusion samples (ten BPEs and ten LA-MPEs). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the profiling results obtained for the discovery set and those obtained for a validation set comprising 42 BPEs and 45 LA-MPEs. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the identified miRNAs and other common tumor markers, such as carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA) 21-1. Microarray profiling showed that miR-198 was significantly downregulated in LA-MPE compared with BPE (p = 0.002). The miRNA microarray analysis results were confirmed by qRT-PCR (p < 0.001) using the validation set. The AUCs for miR-198, CEA and CYFRA 21-1 in the validation set were 0.887, 0.898 and 0.836, respectively. The diagnostic performance of miR-198 was comparable with that of CEA, but better than that of CYFRA 21-1. The AUC for all three markers combined was 0.926 (95% confidence interval, 0.843-0.973) with a sensitivity of 89.2% and a specificity of 85.0%. The present study suggests that cell-free miR-198 from patients with pleural effusion might have diagnostic potential for differentiating LA-MPE from BPE.
循环细胞游离 microRNAs（miRNAs）是潜在的癌症生物标志物。本研究旨在鉴定良性胸腔积液（BPE）和肺癌相关恶性胸腔积液（LA-MPE）之间差异表达的 miRNAs。在 107 例胸腔积液患者中检测了细胞游离 miRNA 的表达水平。采用微阵列技术对 20 例胸腔积液样本（10 例 BPE 和 10 例 LA-MPE）进行了 160 个 miRNA 的筛选。采用实时定量逆转录聚合酶链反应（qRT-PCR）对发现集和包含 42 例 BPE 和 45 例 LA-MPE 的验证集的分析结果进行验证。采用受试者工作特征曲线（ROC）下面积（AUC）评估鉴定的 miRNAs 和其他常见肿瘤标志物（如癌胚抗原（CEA）和细胞角蛋白 19 片段（CYFRA）21-1）的诊断性能。微阵列分析显示，与 BPE 相比，LA-MPE 中 miR-198 显著下调（p=0.002）。采用 qRT-PCR 对验证集进行验证，结果证实了 miRNA 微阵列分析结果（p<0.001）。在验证集中，miR-198、CEA 和 CYFRA 21-1 的 AUC 分别为 0.887、0.898 和 0.836。miR-198 的诊断性能与 CEA 相当，但优于 CYFRA 21-1。三种标志物联合的 AUC 为 0.926（95%置信区间，0.843-0.973），灵敏度为 89.2%，特异性为 85.0%。本研究表明，胸腔积液患者的细胞游离 miR-198 可能具有区分 LA-MPE 和 BPE 的诊断潜力。
