Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.
Birmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham, United Kingdom.
Sci Rep. 2019 Jul 19;9(1):10473. doi: 10.1038/s41598-019-45900-x.
Brain tumours are the most common cause of cancer death in children. Molecular studies have greatly improved our understanding of these tumours but tumour metabolism is underexplored. Metabolites measured in vivo have been reported as prognostic biomarkers of these tumours but analysis of surgically resected tumour tissue allows a more extensive set of metabolites to be measured aiding biomarker discovery and providing validation of in vivo findings. In this study, metabolites were quantified across a range of paediatric brain tumours using H-High-Resolution Magic Angle Spinning nuclear magnetic resonance spectroscopy (HR-MAS) and their prognostic potential investigated. HR-MAS was performed on pre-treatment frozen tumour tissue from a single centre. Univariate and multivariate Cox regression was used to examine the ability of metabolites to predict survival. The models were cross validated using C-indices and further validated by splitting the cohort into two. Higher concentrations of glutamine were predictive of a longer overall survival, whilst higher concentrations of lipids were predictive of a shorter overall survival. These metabolites were predictive independent of diagnosis, as demonstrated in multivariate Cox regression models. Whilst accurate quantification of metabolites such as glutamine in vivo is challenging, metabolites show promise as prognostic markers due to development of optimised detection methods and increasing use of 3 T clinical scanners.
脑肿瘤是儿童癌症死亡的最常见原因。分子研究极大地提高了我们对这些肿瘤的认识，但肿瘤代谢仍未得到充分探索。在体内测量的代谢物已被报道为这些肿瘤的预后生物标志物，但对手术切除的肿瘤组织进行分析可以测量更广泛的代谢物集，有助于发现生物标志物并验证体内发现。在这项研究中，使用 H-高分辨率魔角旋转核磁共振波谱 (HR-MAS) 对一系列儿科脑肿瘤中的代谢物进行了定量，并研究了其预后潜力。HR-MAS 在单个中心的术前冷冻肿瘤组织上进行。单变量和多变量 Cox 回归用于检查代谢物预测生存的能力。使用 C 指数对模型进行交叉验证，并通过将队列分为两部分进行进一步验证。较高的谷氨酰胺浓度与总生存期较长相关，而较高的脂质浓度与总生存期较短相关。这些代谢物在多变量 Cox 回归模型中是独立预测的，而不受诊断的影响。虽然在体内准确定量代谢物（如谷氨酰胺）具有挑战性，但由于优化检测方法的发展和越来越多的使用 3T 临床扫描仪，代谢物作为预后标志物具有广阔的前景。
