循环系统中的肿瘤来源的细胞外囊泡(EV)可能含有肿瘤特异性标志物,体液中的EV检测可能成为早期肿瘤诊断的重要工具,预后评估。脑膜瘤是最常见的良性颅内肿瘤,很少有研究揭示患者体液中脑膜瘤的特异性蛋白标记物。在这项研究中,使用邻近标记技术和非肿瘤患者血浆作为对照,我们检测了脑膜瘤患者手术前后血浆样本中的EV蛋白水平.通过生物信息学分析,我们发现脑膜瘤患者的EV计数和蛋白质计数水平明显高于健康对照组,术后明显下降。在脑膜瘤患者的EV蛋白中,MUC1,SIGLEC11,E-Cadherin,KIT,发现TASCTD2不仅比健康对照组显着升高,但肿瘤切除后也明显下降。此外,使用公开的GEO数据库,我们证实,与正常硬脑膜组织相比,脑膜瘤中MUC1,SIGLEC11和CDH1的mRNA水平显着升高。此外,通过分析这项研究中收集的人类脑膜瘤标本,我们验证了MUC1和SIGLEC11蛋白水平在WHO2级脑膜瘤中显著升高,并与肿瘤增殖水平呈正相关.这项研究表明脑膜瘤分泌EV蛋白进入循环系统,可以作为诊断的特异性标志物,恶性肿瘤预测和肿瘤复发评估。
Tumor derived Extracellular vesicles (EVs) in circulating system may contain tumor-specific markers, and EV detection in body fluids could become an important tool for early tumor diagnosis, prognosis assessment. Meningiomas are the most common benign intracranial tumors, few studies have revealed specific protein markers for meningiomas from patients\' body fluids. In this study, using proximity labeling technology and non-tumor patient plasma as a control, we detected protein levels of EVs in plasma samples from meningioma patients before and after surgery. Through bioinformatics analysis, we discovered that the levels of EV count and protein count in meningioma patients were significantly higher than those in healthy controls, and were significantly decreased postoperatively. Among EV proteins in meningioma patients, the levels of MUC1,
SIGLEC11, E-Cadherin, KIT, and TASCTD2 were found not only significantly elevated than those in healthy controls, but also significantly decreased after tumor resection. Moreover, using publicly available GEO databases, we verified that the mRNA level of MUC1,
SIGLEC11, and CDH1 in meningiomas were significantly higher in comparison with normal dura mater tissues. Additionally, by analyzing human meningioma specimens collected in this study, we validated the protein levels of MUC1 and
SIGLEC11 were significantly increased in WHO grade 2 meningiomas and were positively correlated with tumor proliferation levels. This study indicates that meningiomas secret EV proteins into circulating system, which may serve as specific markers for diagnosis, malignancy predicting and tumor recurrent assessment.