Ica Raluca, Sarbu Mirela, Biricioiu Roxana, Fabris Dragana, Vukelić Željka, Zamfir Alina D
National Institute for Research and Development in Electrochemistry and Condensed Matter, 300224 Timisoara, Romania.
Faculty of Physics, West University of Timisoara, 300223 Timisoara, Romania.
Int J Mol Sci. 2025 Aug 29;26(17):8433. doi: 10.3390/ijms26178433.
Diffuse astrocytoma is a primary brain tumor known for its gradual and diffuse infiltration into the surrounding brain tissue. Given this characteristic, the investigation of the peritumoral region holds potential biological and clinical relevance. In this study, ion mobility spectrometry mass spectrometry (IMS MS) was optimized and applied for the first time for the analysis of gangliosides present in the peritumoral tissue of diffuse astrocytoma. Ganglioside profiling and structural characterization were conducted using high-resolution nanoelectrospray ionization (nanoESI) IMS MS, along with tandem mass spectrometry (MS/MS) via low-energy collision-induced dissociation (CID) in the negative ion mode. Using IMS MS-based separation and screening, we observed a greater diversity of ganglioside species in the peritumoral tissue than previously reported. Notably, an elevated expression was detected for several species, including GT1(d18:1/18:0), GT1(d18:1/20:0), GM2(d18:1/16:2), GD1(d18:1/16:0), GD2(d18:1/20:0), Fuc-GT3(d18:1/24:4), and Fuc-GD1(d18:1/18:2). Although preliminary, these observations prompt consideration of whether these species could be implicated in processes such as microenvironmental modulation, tumor cell infiltration and invasion, maintenance of cellular interactions, or regulation of immune responses. Additionally, their potential utility as biomarkers may merit further exploration. In the subsequent phase of the study, structural analysis using IMS MS, CID tandem MS, and fragmentation data supported the identification of GT1b(d18:1/20:0) isomer in the peritumoral tissue. However, given the exploratory nature of the study and reliance on limited sampling, further investigation across broader sample sets is necessary to extend these findings.
弥漫性星形细胞瘤是一种原发性脑肿瘤，以其逐渐且弥漫性地浸润周围脑组织而闻名。鉴于这一特征，对肿瘤周围区域的研究具有潜在的生物学和临床意义。在本研究中，离子淌度质谱法（IMS MS）首次得到优化并应用于分析弥漫性星形细胞瘤肿瘤周围组织中存在的神经节苷脂。使用高分辨率纳米电喷雾电离（nanoESI）IMS MS以及通过负离子模式下的低能量碰撞诱导解离（CID）进行串联质谱分析（MS/MS），对神经节苷脂进行了谱图分析和结构表征。通过基于IMS MS的分离和筛选，我们观察到肿瘤周围组织中神经节苷脂种类的多样性比先前报道的更大。值得注意的是，检测到几种神经节苷脂种类的表达升高，包括GT1(d18:1/18:0)、GT1(d18:1/20:0)、GM2(d18:1/16:2)、GD1(d18:1/16:0)、GD2(d18:1/20:0)、Fuc-GT3(d18:1/24:4)和Fuc-GD1(d18:1/18:2)。尽管这些观察结果尚属初步，但促使人们考虑这些种类是否可能参与微环境调节、肿瘤细胞浸润和侵袭、细胞间相互作用的维持或免疫反应的调节等过程。此外，它们作为生物标志物的潜在用途可能值得进一步探索。在研究的后续阶段，使用IMS MS、CID串联质谱和碎片数据进行的结构分析支持了在肿瘤周围组织中鉴定出GT1b(d18:1/20:0)异构体。然而，鉴于该研究的探索性质以及对有限样本的依赖，有必要对更广泛的样本集进行进一步研究以扩展这些发现。
