Molecular Nodal Staging Using miRNA Expression in Lung Cancer Patients by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration
Molecular Nodal Staging Using miRNA Expression in Lung Cancer Patients by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration
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DOI：
10.1159/000489178
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发表时间：
2018-01-01
期刊：
影响因子：
3.7
通讯作者：
Yoshino, Ichiro
中科院分区：
文献类型：
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作者：
Inage, Terunaga;Nakajima, Takahiro;Yoshino, Ichiro
背景：超声引导下经支气管针吸（EBUS-TBNA）有限的阴性预测价值经常被讨论。目的：本研究的目的是通过EBUS-TBNA鉴定一种高度敏感的淋巴结分期分子生物标志物。方法：在miRNA表达分析中，选择5种microrna (miRNA) （miR-200a, miR-200b, miR-200c， miR-141和let-7e）作为检测淋巴结转移的候选生物标志物。在为手术切除的淋巴结中区分恶性和良性淋巴结建立了每个标记物的表达切断水平后，将该切断水平应用于快速冷冻的EBUS-TBNA样本。对诱导放化疗后经EBUS-TBNA重新活检的存档的福尔马林固定石蜡包埋（FFPE）样品进行分析。结果：所有候选mirna在转移性淋巴结中的表达均明显高于良性淋巴结（p < 0.05）。miR-200c的诊断率最高，敏感性为95.4%，特异性为100%。将miR-200c的截止值应用于速冻EBUS-TBNA样本时，其敏感性、特异性、阳性预测值、阴性预测值和诊断准确率分别为97.4、81.8、95.0、90.0和94.0%。对于FFPE EBUS-TBNA样本，其敏感性为100，特异性为60.0，阳性预测值为80.0，阴性预测值为100，诊断准确率为84.6%。在重新分期的样本中，4个恶性淋巴结EBUS-TBNA假阴性，但miR-200c准确识别。结论：miR-200c可作为一种高度敏感的分子分期生物标志物，可提高肺癌的淋巴结分期。(C) 2018 S. Karger AG，巴塞尔
Background: The limited negative predictive value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has often been discussed. Objective: The aim of this study was to identify a highly sensitive molecular biomarker for lymph node staging by EBUS-TBNA. Methods: Five microRNAs (miRNAs) (miR-200a, miR-200b, miR-200c, miR-141, and let-7e) were selected as biomarker candidates for the detection of nodal metastasis in a miRNA expression analysis. After having established a cutoff level of expression for each marker to differentiate malignant from benign lymph nodes among surgically dissected lymph nodes, the cutoff level was applied to snap-frozen EBUS-TBNA samples. Archived formalin-fixed paraffin-embedded (FFPE) samples rebiopsied by EBUS-TBNA after induction chemoradiotherapy were also analyzed. Results: The expression of all candidate miRNAs was significantly higher in metastatic lymph nodes than in benign ones (p < 0.05) among the surgical samples. miR-200c showed the highest diagnostic yield, with a sensitivity of 95.4% and a specificity of 100%. When the cutoff value for miR-200c was applied to the snap-frozen EBUS-TBNA samples, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 97.4, 81.8, 95.0, 90.0, and 94.0%, respectively. For restaging FFPE EBUS-TBNA samples, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 100, 60.0, 80.0, 100, and 84.6%, respectively. Among the restaged samples, 4 malignant lymph nodes were false negative by EBUS-TBNA, but they were accurately identified by miR-200c. Conclusions: miR-200c can be used as a highly sensitive molecular staging biomarker that will enhance nodal staging of lung cancer. (C) 2018 S. Karger AG, Basel