Glioblastoma multiforme: Metabolic differences to peritumoral tissue and IDH-mutated gliomas revealed by mass spectrometry imaging
Glioblastoma multiforme: Metabolic differences to peritumoral tissue and IDH-mutated gliomas revealed by mass spectrometry imaging
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DOI：
10.1111/neup.12671
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发表时间：
2020-12-01
期刊：
影响因子：
2.3
通讯作者：
Bednarz, Hanna
中科院分区：
文献类型：
--
作者：
Kampa, Judith M.;Kellner, Udo;Bednarz, Hanna
多形性胶质母细胞瘤（GBM）是最常见的恶性原发性脑肿瘤。高浸润率和不良治疗反应使其成为最致命的胶质瘤。肿瘤代谢与正常代谢不同，受多种因素影响，可延长生存期。代谢物是显示组织中代谢途径的小分子（< 1500 Da）。为了确定人GBMs肿瘤和瘤周组织之间的代谢变化，我们对25个切除肿瘤的薄片进行了质谱成像（MSI）。此外，还将GBMs与6个异柠檬酸脱氢酶（IDH1）基因（IDH1）突变的胶质瘤进行了比较。使用这种技术，可以很容易地在单个组织切片上看到多种分析物。使用高分辨率MSI根据代谢物的准确质量进行注释。对其在肿瘤和肿瘤周围区域的平均强度差异进行统计评估，并在组织上显示丰度。肿瘤区域抗坏血酸、牛磺酸和谷胱甘肽水平的提高表明对肿瘤有保护作用。GBM区域嘌呤和嘧啶代谢化合物水平升高表明能量需求高。根据这些结果，检测到乳酸和谷氨酰胺的丰度增加。此外，在肿瘤区域测量到n -乙酰天冬氨酸丰度下降，n -乙酰天冬氨酸是神经元健康的标志。获得的代谢信息可以潜在地支持和个性化治疗方法，因此强调了MSI在GBM研究中的适用性。
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor. High infiltration rates and poor therapy responses make it the deadliest glioma. The tumor metabolism is known to differ from normal one and is influenced through various factors which can lead to longer survival. Metabolites are small molecules (< 1500 Da) that display the metabolic pathways in the tissue. To determine the metabolic alterations between tumor and peritumoral tissue in human GBMs, mass spectrometry imaging (MSI) was performed on thin sections from 25 resected tumors. In addition, the GBMs were compared with six gliomas harboring a mutation in the isocitrate dehydrogenase (IDH1) gene (IDH1). With this technique, a manifold of analytes can be easily visualized on a single tissue section. Metabolites were annotated based on their accurate mass using high resolution MSI. Differences in their mean intensities in the tumor and peritumoral areas were statistically evaluated and abundances were visualized on the tissue. Enhanced levels of the antioxidants ascorbic acid, taurine, and glutathione in tumor areas suggest protective effects on the tumor. Increased levels of purine and pyrimidine metabolism compounds in GBM areas indicate the high energy demand. In accordance with these results, enhanced abundances of lactate and glutamine were detected. Moreover, decreased abundance of N-acetylaspartate, a marker for neuronal health, was measured in tumor areas. Obtained metabolic information could potentially support and personalize therapeutic approaches, hence emphasizing the suitability of MSI for GBM research.