In this study, we evaluated the diagnostic value and molecular characteristics of plasma extracellular vesicles (EVs)-derived miRNAs for patients with solitary pulmonary nodules (SPNs), particularly ground-glass nodules (GGNs). This study was registered at www.clinicaltrials.gov under registration number NCT03230019. Small RNA sequencing was performed to assess plasma EVs miRNAs in 59 patients, including 12 patients with benign nodules (2017, training set). MiRNA profiles of 40 an additional individuals were sequenced (2018, validation set). Overall, 16 pure GGNs, 21 mixed GGNs, and 42 solid nodules were included, with paired post-operative plasma samples available for 20 patients. The target miRNA/reference miRNA ratio was used to construct a support vector machine (SVM) model. The SVM model with the best specificity showed 100% specificity in both the training and validation sets independently. The model with the best sensitivity showed 100% and 96.9% sensitivity in the training and validation sets, respectively. Principal component analysis revealed that pure GGN distributions were distinct from those of solid nodules, and mixed GGNs had a diffuse distribution. Among differentially expressed miRNAs, miR-500a-3p, miR-501-3p, and miR-502-3p were upregulated in tumor tissues and enhanced overall survival. The SVM classifier accurately distinguished malignant GGNs and benign nodules. The distinct profile characteristics of miRNAs provided insights into the feasibility of EVs miRNAs as prognostic factors in lung cancer.

在这项研究中，我们评估了血浆细胞外囊泡（EVs）产生的miRNA对孤立性肺结节（SPN），特别是毛玻璃结节（GGN）患者的诊断价值和分子特征。该研究已在www.clinicaltrials.gov上注册，注册号为NCT03230019。进行了小分子RNA测序以评估59例患者的血浆EVs miRNA，包括12例良性结节患者（2017年，培训集）。对另外40个人的MiRNA谱进行了测序（2018，验证集）。总体上，包括16个纯GGN，21个混合GGN和42个实体结节，并为20例患者提供了成对的术后血浆样品。靶标miRNA /参考miRNA比率用于构建支持向量机（SVM）模型。具有最佳特异性的SVM模型在训练集和验证集中均显示100％的特异性。灵敏度最高的模型在训练和验证集中分别显示100％和96.9％的灵敏度。主成分分析表明，纯GGN的分布不同于固体结节，而混合GGN则具有分散分布。在差异表达的miRNA中，miR-500a-3p，miR-501-3p和miR-502-3p在肿瘤组织中上调并提高了总生存期。SVM分类器可准确地区分恶性GGN和良性结节。miRNA的独特特征为EVs miRNA作为肺癌预后因素的可行性提供了见识。