作为早期 NSCLC 患者预后生物标志物的循环无细胞和细胞外囊泡衍生 microRNA:RESTING 研究的结果。

IF 11.4 1区 医学 Q1 ONCOLOGY
Elisabetta Petracci, Luigi Pasini, Milena Urbini, Enriqueta Felip, Franco Stella, Fabio Davoli, Maurizio Salvi, Michele Beau-Faller, Michela Tebaldi, Irene Azzali, Matteo Canale, Piergiorgio Solli, Giulia Lai, Ramon Amat, Caterina Carbonell, Pierre-Emmanuel Falcoz, Alex Martinez-Marti, Erwan Pencreach, Angelo Delmonte, Lucio Crinò, Paola Ulivi
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引用次数: 0

摘要

背景:目前仍需要对早期非小细胞肺癌(NSCLC)患者进行准确分层,以确定不同的预后组别。本研究旨在探讨:1)循环无细胞(CF)和细胞外囊泡(EVs)衍生的微RNA(miRNAs)的预后潜力;2)它们相对于已知预后因素(PFs)的附加值:RESTING研究是一项多中心前瞻性观察性队列研究,对象是切除的IA-IIIA期NSCLC患者。主要终点是无病生存期(DFS),主要分析分别针对CF-和EV-miRNA。研究人员从血浆中分离出CF-和EV-miRNA,制备了miRNA特异性文库并进行了测序。为了达到研究目的,我们建立了三个统计模型:一个是仅使用 miRNA 数据的模型(模型 1);一个是同时使用 miRNA 和已知 PFs(年龄、性别和病理分期)的模型(模型 2);一个是仅使用 PFs 的模型(模型 3)。采用五倍交叉验证(CV)来评估每种模型的预测性能。使用了标准 Cox 回归和弹性净正则化 Cox 回归:共有 222 名患者入选。中位随访时间为 26.3(95% CI 25.4-27.6)个月。在模型 1 中,3 个 CF-miRNA 和 21 个 EV-miRNA 与 DFS 相关。在模型2中,2个CF-miRNA(miR-29c-3p和miR-877-3p)和5个EV-miRNA(miR-181a-2-3p、miR-182-5p、miR-192-5p、miR-532-3p和miR-589-5p)仍与DFS相关。从通路富集分析来看,TGF-beta和NOTCH是参与度最高的通路:这项研究发现了有希望的预后CF-和EV-miRNA,它们可作为一种非侵入性、经济有效的工具来帮助临床决策。不过,有必要在外部患者队列中进一步评估所获得的 miRNA。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circulating cell-free and extracellular vesicles-derived microRNA as prognostic biomarkers in patients with early-stage NSCLC: results from RESTING study.

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

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来源期刊
CiteScore
18.20
自引率
1.80%
发文量
333
审稿时长
1 months
期刊介绍: The Journal of Experimental & Clinical Cancer Research is an esteemed peer-reviewed publication that focuses on cancer research, encompassing everything from fundamental discoveries to practical applications. We welcome submissions that showcase groundbreaking advancements in the field of cancer research, especially those that bridge the gap between laboratory findings and clinical implementation. Our goal is to foster a deeper understanding of cancer, improve prevention and detection strategies, facilitate accurate diagnosis, and enhance treatment options. We are particularly interested in manuscripts that shed light on the mechanisms behind the development and progression of cancer, including metastasis. Additionally, we encourage submissions that explore molecular alterations or biomarkers that can help predict the efficacy of different treatments or identify drug resistance. Translational research related to targeted therapies, personalized medicine, tumor immunotherapy, and innovative approaches applicable to clinical investigations are also of great interest to us. We provide a platform for the dissemination of large-scale molecular characterizations of human tumors and encourage researchers to share their insights, discoveries, and methodologies with the wider scientific community. By publishing high-quality research articles, reviews, and commentaries, the Journal of Experimental & Clinical Cancer Research strives to contribute to the continuous improvement of cancer care and make a meaningful impact on patients' lives.
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