Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.

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Introduction: Current nodal staging of NSCLC is defined only by anatomical location of lymph nodes (LNs). The aim of this study is to investigate prognostic impacts of the number of metastatic LNs by stratifying the present N classification. Methods: We analyzed 1989 patients with NSCLC who underwent complete resection by lobectomy or pneumonectomy involving dissection of the hilar and mediastinal LNs from 2003 to 2012. We classified patients according to the number of metastatic nodes and stations and their current category of metastatic LNs. We analyzed the overall survival in each group and assessed the survival impact of the combination of them. Results: In the multivariate analyses of all patients, pathological N1 (pN1) (reference [ref.] pN2) and single-node metastasis (ref. multiple-node) were independent prognostic factors whereas single-station metastasis (ref. multiple-station) was not. In the respective multivariate analyses of pN1 and pN2 disease, multiple-node metastasis (ref. single-node) was an independent prognostic factor in pN1 disease (hazard ratio: 1.41, p ¼ 0.04), but not in pN2 disease. Investigation for other boundaries of a number of metastatic LNs of three or more (ref. one to two), four or more (ref. one to three), and five or more (ref. one to four) found that all of them were independent prognostic factors in both pN1 and pN2 diseases. Conclusions: The number of metastatic LNs had a strong impact on survival in addition to the current pN classification. To clarify its prognostic impact, further study is needed in other datasets including patients treated by nonsurgical modalities.

Our series showed some characteristic US patterns of EC. A good understanding of its US findings and appropriate emergent management will reduce the serious morbidity and mortality rates caused by EC.

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