Oncology. 2018;94(5):311-323. doi: 10.1159/000487006. Epub 2018 Mar 13.
The aim of this study was to clarify the usefulness of plasma exosomal microRNA-451a (miR-451a) as a novel biomarker for the early prediction of recurrence and prognosis in non-small cell lung cancer (NSCLC) patients after curative resection.
Before surgery, plasma samples were collected and exosomal microRNA (miRNA) levels were evaluated. We first profiled specific exosomal miRNAs related to recurrence in 6 NSCLC patients with stage IA cancer by miRNA microarray. We then validated the usefulness of selected miRNAs as biomarkers using the other 285 NSCLC patients.
Plasma exosomal miR-451a showed the highest upregulation in the NSCLC patients with recurrence in the miRNA microarray analysis. A significant positive correlation was demonstrated between exosomal miR-451a levels and NSCLC tissue miR-451a levels. Exosomal miR-451a showed a significant association with lymph node metastasis, vascular invasion, and stage. In stage I, II, or III patients, the overall survival (OS) and disease-free survival (DFS) rates among the high-exosomal-miR-451a patients were significantly worse than those among the low-exosomal-miR-451a patients. In Cox multivariate analysis, exosomal miR-451a showed significance for OS and DFS.
Plasma exosomal miR-451a might serve as a reliable biomarker for the prediction of recurrence and prognosis in NSCLC patients with stage I, II, or III cancer.
本研究旨在阐明血浆外泌体 microRNA-451a（miR-451a）作为一种新型生物标志物在非小细胞肺癌（NSCLC）患者根治性切除术后早期预测复发和预后的有用性。
在手术前收集血浆样本并评估外泌体 microRNA（miRNA）水平。我们首先通过 miRNA 微阵列分析了 6 例 I 期 NSCLC 患者与复发相关的特定外泌体 miRNA，然后使用其他 285 例 NSCLC 患者验证了选定 miRNA 作为生物标志物的有用性。
miRNA 微阵列分析显示，血浆外泌体 miR-451a 在复发的 NSCLC 患者中上调最高。外泌体 miR-451a 水平与 NSCLC 组织 miR-451a 水平之间存在显著正相关。外泌体 miR-451a 与淋巴结转移、血管侵犯和分期显著相关。在 I 期、II 期或 III 期患者中，高外泌体 miR-451a 患者的总生存率（OS）和无病生存率（DFS）明显差于低外泌体 miR-451a 患者。在 Cox 多变量分析中，外泌体 miR-451a 对 OS 和 DFS 有意义。
血浆外泌体 miR-451a 可能作为一种可靠的生物标志物，用于预测 I 期、II 期或 III 期 NSCLC 患者的复发和预后。
