Wang Weiwei, Liu Na, Wang Shanshan, Yu Chunkai, Pan Lei, Zhang Man
Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Clin Proteomics. 2025 Aug 25;22(1):30. doi: 10.1186/s12014-025-09554-4.
Small cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis. This study aimed to analyze the urinary exosomal proteome of SCLC patients to identify and validate potential non-invasive biomarkers for improving diagnosis, treatment response monitoring, and prognosis prediction.
We analyzed 90 urine samples from SCLC patients, divided into training (n = 38) and validation (n = 52) sets, including untreated, partial/complete remission, and relapsed groups. Ten healthy controls were included. Urinary exosomes were isolated by ultracentrifugation. The proteomic analysis employed data-independent acquisition mass spectrometry (DIA-MS) and parallel reaction monitoring (PRM). Immunohistochemistry was performed on 30 pairs of SCLC and adjacent normal tissues.
Proteomic analysis revealed distinct exosomal protein expression patterns across SCLC stages. RAB11A emerged as a key differentially expressed protein. PRM validation confirmed significant changes in RAB11A levels across disease stages. ROC curve analysis demonstrated excellent diagnostic performance of RAB11A in distinguishing SCLC patients from healthy controls (AUC = 0.91, 95% CI 0.79-1.00, P = 0.0004), with a sensitivity of 85% and specificity of 92%. RAB11A also showed significant potential in monitoring treatment response (AUC = 0.86, 95% CI 0.69-1.00, P = 0.0019) and disease relapse (AUC = 0.90, 95% CI 0.76-1.00, P = 0.0005). Immunohistochemistry showed significantly higher RAB11A expression in SCLC tissues compared to adjacent normal tissues (70% vs. 33% positive expression, P = 0.043).
Urinary exosomal RAB11A shows promise as a non-invasive biomarker for SCLC diagnosis, treatment response monitoring, and early detection of relapse, potentially improving clinical management of SCLC patients. The findings provide insights into SCLC pathogenesis and offer a non-invasive approach for patient monitoring, which could improve clinical management strategies.
小细胞肺癌（SCLC）是一种侵袭性恶性肿瘤，预后较差。本研究旨在分析SCLC患者的尿液外泌体蛋白质组，以鉴定和验证潜在的非侵入性生物标志物，用于改善诊断、治疗反应监测和预后预测。
我们分析了90份SCLC患者的尿液样本，分为训练集（n = 38）和验证集（n = 52），包括未治疗、部分/完全缓解和复发组。纳入了10名健康对照。通过超速离心分离尿液外泌体。蛋白质组分析采用数据非依赖采集质谱（DIA-MS）和平行反应监测（PRM）。对30对SCLC组织和相邻正常组织进行免疫组织化学检测。
蛋白质组分析揭示了SCLC各阶段不同的外泌体蛋白表达模式。RAB11A成为关键的差异表达蛋白。PRM验证证实了RAB11A水平在疾病各阶段的显著变化。ROC曲线分析表明，RAB11A在区分SCLC患者和健康对照方面具有出色的诊断性能（AUC = 0.91，95%CI 0.79 - 1.00，P = 0.0004），敏感性为85%，特异性为92%。RAB11A在监测治疗反应（AUC = 0.86，95%CI 0.69 - 1.00，P = 0.0019）和疾病复发（AUC = 0.90，95%CI 0.76 - 1.00，P = 0.0005）方面也显示出显著潜力。免疫组织化学显示，与相邻正常组织相比，SCLC组织中RAB11A表达显著更高（阳性表达率70%对33%，P = 0.043）。
尿液外泌体RAB11A有望作为SCLC诊断、治疗反应监测和复发早期检测以及改善SCLC患者临床管理的非侵入性生物标志物。这些发现为SCLC发病机制提供了见解，并为患者监测提供了一种非侵入性方法，可改善临床管理策略。
