Cooper Medical School, Rowan University, Camden, NJ, USA.
College of Medicine, University of Florida, Gainesville, FL, USA.
Brain Tumor Pathol. 2023 Apr;40(2):101-108. doi: 10.1007/s10014-023-00455-8. Epub 2023 Apr 11.
Oligodendrogliomas are a type of rare and incurable gliomas whose metabolic profiles have yet to be fully examined. The present study examined the spatial differences in metabolic landscapes underlying oligodendrogliomas and should provide unique insights into the metabolic characteristics of these uncommon tumors. Single-cell RNA-sequencing expression profiles from 4044 oligodendroglioma cells derived from tumors resected from four locations frontal, temporal, parietal, and frontotemporoinsular) and in which 1p/19q co-deletion and IDH1 or IDH2 mutations were confirmed were computationally analyzed through a robust workflow to elucidate relative differences in metabolic pathway activities among the different locations. Dimensionality reduction using metabolic expression profiles exhibited clustering corresponding to each location subgroup. From the 80 metabolic pathways examined, over 70 pathways had significantly different activity scores between location subgroups. Further analysis of metabolic heterogeneity suggests that mitochondrial oxidative phosphorylation accounts for considerable metabolic variation within the same locations. Steroid and fatty acid metabolism pathways were also found to be major contributors to heterogeneity. Oligodendrogliomas display distinct spatial metabolic differences in addition to intra-location metabolic heterogeneity.
少突胶质细胞瘤是一种罕见且无法治愈的神经胶质瘤，其代谢特征尚未被充分研究。本研究检测了源于额叶、颞叶、顶叶和额颞顶枕叶四个部位切除肿瘤的 4044 个少突胶质细胞瘤细胞的代谢景观的空间差异，这应该为这些罕见肿瘤的代谢特征提供独特的见解。通过稳健的工作流程对经计算分析确认 1p/19q 共缺失和 IDH1 或 IDH2 突变的肿瘤中 4044 个少突胶质细胞瘤细胞的单细胞 RNA 测序表达谱进行分析，以阐明不同部位之间代谢途径活性的相对差异。使用代谢表达谱进行降维，表现出与每个位置亚组相对应的聚类。在所检查的 80 条代谢途径中，有 70 多条途径在位置亚组之间的活性评分存在显著差异。对代谢异质性的进一步分析表明，线粒体氧化磷酸化是同一部位内代谢变异的主要原因。固醇和脂肪酸代谢途径也是异质性的主要贡献者。除了位置内的代谢异质性外，少突胶质细胞瘤还表现出明显的空间代谢差异。
