非小细胞肺癌（NSCLC）仍然是全球癌症相关死亡的主要原因，这主要是由于其转移倾向。诊断为局部原发癌的患者比转移癌患者的生存率更高。因此，必须发现用于早期检测 NSCLC 和及时预测肿瘤转移的生物标志物，以改善患者的预后。在这里，我们利用综合方法来分离和表征 NSCLC 患者以及健康个体的血浆外泌体。然后，我们进行了蛋白质组学分析和平行反应监测，以识别和验证血浆外泌体中排名最高的蛋白质。我们的研究表明，转移的 NSCLC 患者的外泌体中的蛋白质组与健康个体的蛋白质组明显不同。前者比后者具有更大的直径和更低的外泌体浓度。此外，在 1220 个已鉴定的外泌体蛋白中，我们鉴定了两个不同的生物标志物组。第一个生物标志物组（FGB、FGG 和 VWF）显示出早期 NSCLC 诊断的潜力，并证明与 NSCLC 患者的生存时间直接相关。第二组生物标志物（CFHR5、C9 和 MBL2）成为评估 NSCLC 转移的潜在生物标志物，其中单独的 CFHR5 与 NSCLC 患者的总体生存率显着相关。这些发现强调了血浆外泌体生物标志物用于早期 NSCLC 诊断的潜力和转移预测。值得注意的是，CFHR5 是 NSCLC 患者有希望的预后指标。外泌体生物标志物的临床应用为增强 NSCLC 的治疗提供了潜力。© 2023。作者。

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes.Here, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes.Our study revealed that the proteome in exosomes from NSCLC patients with metastasis was distinctly different from that from healthy individuals. The former had larger diameters and lower concentrations of exosomes than the latter. Furthermore, among the 1220 identified exosomal proteins, we identified two distinct panels of biomarkers. The first panel of biomarkers (FGB, FGG, and VWF) showed potential for early NSCLC diagnosis and demonstrated a direct correlation with the survival duration of NSCLC patients. The second panel of biomarkers (CFHR5, C9, and MBL2) emerged as potential biomarkers for assessing NSCLC metastasis, of which CFHR5 alone was significantly associated with the overall survival of NSCLC patients.These findings underscore the potential of plasma exosomal biomarkers for early NSCLC diagnosis and metastasis prediction. Notably, CFHR5 stands out as a promising prognostic indicator for NSCLC patients. The clinical utility of exosomal biomarkers offers the potential to enhance the management of NSCLC.© 2023. The Author(s).