Department of Internal Medicine, Cheongju St. Mary Hospital, Cheongju, Korea.
Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Korea.
Cancer Res Treat. 2014 Apr;46(2):178-85. doi: 10.4143/crt.2014.46.2.178. Epub 2014 Apr 22.
The accurate and timely diagnosis of malignant pleural effusion (MPE) in lung cancer patients is important because MPE has a poor prognosis and is classified as stage IV disease. Molecular biomarkers for pleural effusion, such as circulating extracellular microRNAs (miRNAs) isolated from pleural fluid, may help in the diagnosis of MPE. The present study examined whether miRNAs that are deregulated in lung cancer (miR-134, miR-185, and miR-22) can serve as diagnostic markers for lung adenocarcinoma-associated MPE (LA-MPE).
Real-time reverse transcription quantitative polymerase chain reaction was used to measure the expression of the three miRNAs in samples from 87 patients with pleural effusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs). The area under the receiver operating characteristic curve (AUC) was then used to evaluate the diagnostic performance of each of the three miRNAs and compare it with that of the common tumor marker, carcinoembryonic antigen (CEA).
The expression of all three miRNAs was significantly lower in LA-MPE than in BPE (p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882, 0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased the diagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864 to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%.
The present study suggests that the expression levels of circulating extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may have diagnostic value when differentiating between LA-MPE and BPE.
准确及时地诊断肺癌患者的恶性胸腔积液(MPE)非常重要,因为 MPE 预后不良,被归类为 IV 期疾病。胸腔积液中分离出的循环细胞外 microRNAs(miRNAs)等胸腔积液中的分子生物标志物可能有助于 MPE 的诊断。本研究探讨了失调的肺癌 miRNA(miR-134、miR-185 和 miR-22)是否可以作为肺腺癌相关 MPE(LA-MPE)的诊断标志物。
采用实时逆转录定量聚合酶链反应(PCR)检测 87 例胸腔积液患者(包括 45 例 LA-MPE 和 42 例良性胸腔积液(BPE))样本中三种 miRNA 的表达。然后使用受试者工作特征曲线(ROC)下面积(AUC)评估三种 miRNA 各自的诊断性能,并与常见肿瘤标志物癌胚抗原(CEA)进行比较。
LA-MPE 中三种 miRNA 的表达均明显低于 BPE(p<0.001)。miR-134、miR-185、miR-22 和 CEA 的 AUC 分别为 0.721、0.882、0.832 和 0.898。将 CEA 与三种 miRNA 结合使用可提高诊断性能,AUC 为 0.942(95%置信区间:0.864-0.982),灵敏度为 91.9%,特异性为 92.5%。
本研究表明,胸腔积液患者循环细胞外 miR-134、miR-185 和 miR-22 的表达水平在区分 LA-MPE 和 BPE 时可能具有诊断价值。