仍需要将早期非小细胞肺癌 (NSCLC) 患者准确分层为不同预后组的因素。本研究旨在调查 1) 循环游离细胞 (CF) 和细胞外囊泡 (EV) 衍生的 microRNA (miRNA) 的预后潜力，以及 2) 它们相对于已知预后因素 (PF) 的附加值。RESTING 研究是一项针对已切除的 IA-IIIA 期 NSCLC 患者的多中心前瞻性观察队列研究。主要终点是无病生存期 (DFS)，主要分析分别针对 CF-和 EV-miRNA 进行。从血浆中分离出 CF-和 EV-miRNA，并制备 miRNA 特异性文库并进行测序。为了达到研究目标，指定了三种统计模型：一种仅使用 miRNA 数据（模型 1）；另一种使用 miRNA 数据（模型 1）。一种同时使用 miRNA 和已知的 PF（年龄、性别和病理阶段）（模型 2），另一种仅使用 PF（模型 3）。五折交叉验证（CV）用于评估每个的预测性能。采用标准Cox回归和弹性网正则化Cox回归。共有222名患者入组。中位随访时间为 26.3 (95% CI 25.4-27.6) 个月。从模型 1 中，3 个 CF-miRNA 和 21 个 EV-miRNA 与 DFS 相关。在模型 2 中，两个 CF-miRNA（miR-29c-3p 和 miR-877-3p）和五个 EV-miRNA（miR-181a-2-3p、miR-182-5p、miR-192-5p、miR-532） -3p 和 miR-589-5p) 仍然与 DFS 相关。从通路富集分析来看，TGF-β 和 NOTCH 是参与最多的通路。这项研究发现了有前途的预后 CF- 和 EV-miRNA，可用作非侵入性、经济有效的工具来辅助临床决策。然而，有必要对外部患者队列中获得的 miRNA 进行进一步评估。© 2024。作者。

Factors to accurately stratify patients with early-stage non-small cell lung cancer (NSCLC) in different prognostic groups are still needed. This study aims to investigate 1) the prognostic potential of circulating cell-free (CF) and extracellular vesicles (EVs)-derived microRNA (miRNAs), and 2) their added value with respect to known prognostic factors (PFs).The RESTING study is a multicentre prospective observational cohort study on resected stage IA-IIIA patients with NSCLC. The primary end-point was disease-free survival (DFS), and the main analyses were carried out separately for CF- and EV-miRNAs. CF- and EV-miRNAs were isolated from plasma, and miRNA-specific libraries were prepared and sequenced. To reach the study aims, three statistical models were specified: one using the miRNA data only (Model 1); one using both miRNAs and known PFs (age, gender, and pathological stage) (Model 2), and one using the PFs alone (Model 3). Five-fold cross-validation (CV) was used to assess the predictive performance of each. Standard Cox regression and elastic net regularized Cox regression were used.A total of 222 patients were enrolled. The median follow-up time was 26.3 (95% CI 25.4-27.6) months. From Model 1, three CF-miRNAs and 21 EV-miRNAs were associated with DFS. In Model 2, two CF-miRNAs (miR-29c-3p and miR-877-3p) and five EV-miRNAs (miR-181a-2-3p, miR-182-5p, miR-192-5p, miR-532-3p and miR-589-5p) remained associated with DFS. From pathway enrichment analysis, TGF-beta and NOTCH were the most involved pathways.This study identified promising prognostic CF- and EV-miRNAs that could be used as a non-invasive, cost-effective tool to aid clinical decision-making. However, further evaluation of the obtained miRNAs in an external cohort of patients is warranted.© 2024. The Author(s).