PO.CL01.20 · 临床研究
针对儿童高级别胶质瘤的新型基于细胞外囊泡的生物标志物方法的开发
Development of a novel extracellular vesicle-based biomarker approach for pediatric high-grade glioma
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
儿童高级别胶质瘤（pHGG）占儿童脑肿瘤的 20%，且与较差的生存率相关。目前，pHGG 的检测依赖于磁共振成像（MRI），这是一种昂贵且耗时的检查。细胞外囊泡（EV）携带指示其细胞来源的分子标志物，并可从多种生物体液中分离出来，提供了一种替代方法。近期研究表明，pHGG 含有在分子和形态上类似于放射状胶质细胞（RG，一种神经祖细胞）的细胞。鉴于 RG 通常仅存在于发育中的大脑，我们假设从 RG 样胶质瘤细胞分泌的 EV（RG-EV）可作为 pHGG 的生物标志物。然而，目前尚无既定的分子标志物能够特异性地检测 RG 来源的 EV。为解决这一问题，我们首先确定了一组表面标志物的组合，以区分源自 RG 样胶质瘤细胞的 EV 与非 RG 细胞的 EV。随后我们在患者来源的细胞系中验证了这些标志物的表达。我们对 EV 的分析显示，与人类星形胶质细胞相比，pHGG 细胞分泌的 RG-EV 比例显著更高（88.88 ± 7.69% 对 0.57 ± 0.28%；p < 0.0001），同时还伴有其他肿瘤相关标志物，包括嵌合抗原受体（CAR）T 细胞疗法的靶点，如双唾液酸神经节苷脂 GD2（73.46 ± 11.75% 对 0.32 ± 0.07%；p < 0.001）。综上所述，我们的研究结果表明，RG 来源的 EV 可通过该标志物组合被特异性地分离和检测，从而将 pHGG 细胞与非恶性星形胶质细胞区分开来。这项工作为开发一种针对 pHGG 的新型基于 EV 的诊断性生物标志物方法奠定了基础。
查看英文原文 English abstract
Pediatric high-grade gliomas (pHGGs) account for 20% of childhood brain tumors and are associated with poor survival rates. Currently, pHGG detection relies on Magnetic Resonance Imaging (MRI), a costly and time-consuming procedure. Extracellular vesicles (EVs) carry molecular markers indicative of their cellular origin and can be isolated from various biofluids, offering an alternative approach. Recent studies showed that pHGGs contain cells that molecularly and morphologically resemble radial glia (RG), a type of neural progenitor. Given that RGs are normally exclusive to the developing brain, we hypothesized that EVs secreted from RG-like glioma cells (RG-EV) serve as a pHGG biomarker. However, there are no established molecular markers to specifically detect RG-derived EVs. To address this, we first identified a combination of surface markers to differentiate EVs derived from RG-like glioma cells from those of non-RG cells. We next validated the expression of these markers in patient-derived cell lines. Our analysis of EVs showed that pHGG cells secrete a significantly higher proportion of RG-EV compared to human astrocytes (88.88 ± 7.69% vs 0.57 ± 0.28%; p < 0.0001), along with other tumor-associated markers, including targets of chimeric antigen receptor (CAR) T cell therapy such as disialoganglioside GD2 (73.46 ± 11.75% vs 0.32 ± 0.07%; p < 0.001). Taken together, our findings showed that RG-derived EVs can be specifically isolated and detected by the combination of markers, distinguishing pHGG cells from non-malignant astrocytes. This work establishes a basis for developing a novel EV-based diagnostic biomarker approach for pHGGs.
利益披露 Disclosure
A. Fernandez Garcia, None..
P. Iyer, None..
P. Ashi, None..
K. Funato, None.