CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China.
Department of Chemistry , Tsinghua University , Beijing , 100084 , China.
Anal Chem. 2019 Aug 6;91(15):9580-9589. doi: 10.1021/acs.analchem.9b00914. Epub 2019 Jul 18.
The invasiveness evaluation of nonfunctional pituitary adenoma (NFPAs) is crucial for the prediction of the malignant potential and for making surgical plans of NFPAs. Current invasiveness evaluation of NFPAs is based on neuroimaging, which can hardly predict the invasive potential and dynamically monitor disease progress. Here we used microbead-assisted flow cytometry to detect and analyze the serum extracellular vesicles (EVs) from 30 NFPAs patients (15 invasive and 15 noninvasive). Lower expressions of folate receptor 1 (FOLR1) and epithelial cell adhesion molecule (EpCAM) were found in serum EVs from the invasive NFPAs patients compared to the noninvasive ones [area under the curve (AUC) of 0.94 for FOLR1 and 0.88 for EpCAM]. Meanwhile, increased mRNA expression of vimentin and N-cadherin, two mesenchymal markers, was found in serum EVs from the invasive NFPAs patients compared to the noninvasive ones. Consistent results were observed in the tumor tissue that invasive NFPAs have lower expression of the epithelial markers while higher expression of the mesenchymal markers. These results suggested the possible role of epithelial-mesenchymal transition (EMT) in the invasiveness of NFPAs. Pituitary tumor transforming gene 1 () mRNA in serum EVs was also found to be an indicator for invasive NFPAs and is related with EMT. These results provide a method for the blood-based diagnosis and invasiveness evaluation of NFPAs and would be beneficial to the diagnosis, prognosis prediction, and surgical risk evaluation of NFPAs.
无功能性垂体腺瘤（NFPAs）的侵袭性评估对于预测恶性潜能和制定 NFPAs 的手术计划至关重要。目前，NFPAs 的侵袭性评估基于神经影像学，很难预测侵袭潜能并进行动态监测疾病进展。在这里，我们使用微珠辅助流式细胞术检测和分析了 30 名 NFPAs 患者（15 名侵袭性和 15 名非侵袭性）的血清细胞外囊泡（EVs）。与非侵袭性 NFPAs 患者相比，侵袭性 NFPAs 患者血清 EVs 中的叶酸受体 1（FOLR1）和上皮细胞黏附分子（EpCAM）表达水平较低[FOLR1 的曲线下面积（AUC）为 0.94，EpCAM 为 0.88]。同时，与非侵袭性 NFPAs 患者相比，侵袭性 NFPAs 患者血清 EVs 中的间充质标志物波形蛋白和 N-钙黏蛋白的 mRNA 表达增加。在侵袭性 NFPAs 肿瘤组织中也观察到了一致的结果，即侵袭性 NFPAs 的上皮标志物表达降低，而间充质标志物表达升高。这些结果表明上皮-间质转化（EMT）可能在 NFPAs 的侵袭性中起作用。还发现血清 EVs 中的垂体瘤转化基因 1 () mRNA 是侵袭性 NFPAs 的标志物，与 EMT 有关。这些结果为 NFPAs 的基于血液的诊断和侵袭性评估提供了一种方法，有助于 NFPAs 的诊断、预后预测和手术风险评估。
