What can metabolites tell us about gliomas?
What can metabolites tell us about gliomas?
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关于神经胶质瘤，代谢物能告诉我们什么？
DOI：
10.1093/neuonc/noac128
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发表时间：
2022
期刊：
影响因子：
15.9
通讯作者：
Saya Hideyuki
中科院分区：
文献类型：
--
作者：
Sampetrean Oltea;Saya Hideyuki
癌细胞的不受控制的增殖需要相应的代谢调节。因此，生物能代谢失调被认为是恶性肿瘤的核心特征。在过去的十年中，这一观点在不同类型的肿瘤中得到了广泛的验证，对其分子基础的理解也有了相当大的进展，部分原因是代谢组学的力量。沿着肿瘤代谢物的鉴定，如（R）-2-羟基戊二酸（R-2-HG），3代谢组学研究揭示了肿瘤特异性特征，为癌症表型提供了新的机制见解，并增强了我们对药物作用的理解。4正如本期《神经肿瘤学》所报道的，Björkblom等人5使用多平台代谢组学来扩展我们与胶质瘤代谢相关的知识。作者采用气相色谱-液相色谱-质谱联用技术（GC-MS和LC-MS）分析了大量成人胶质瘤（n= 224）的特征。对1132种代谢特征进行定量，鉴定出240种独特的代谢物，并将其与遗传、临床和病理分析相结合，从而提供了WHO分类的六种成人胶质瘤亚型的代谢表型的综合视图。该研究的一个关键发现是异柠檬酸脱氢酶（IDH）野生型肿瘤（n= 172）和IDH突变型肿瘤（n= 52）具有显著不同的代谢谱，即使从分析中排除IDH突变肿瘤中高水平存在的2-HG。虽然这个结果看起来并不令人惊讶，但它有几个有趣的含义。肿瘤代谢具有细胞自主的核心，但它也受到外部因素的高度影响，进而影响微环境。自主决定因素包括遗传畸变和致癌基因成瘾，而环境驱动的影响可以追溯到营养和氧气的供应以及与非癌细胞以及细胞外基质的相互作用。6 WHO分类的成人胶质瘤亚型具有不同的代谢谱的事实表明，每种亚型的细胞代谢组分具有稳健性和特异性，并证实代谢表型作为主要代谢组分的潜力。
The uncontrolled proliferation of cancer cells requires corresponding metabolic adjustments. A deregulated bioenergetic metabolism is thus considered a core feature of malignant neoplasms. 1, 2 This viewpoint has been extensively validated 2 in different types of tumors over the past decade, and the understanding of its molecular foundation has advanced considerably, in part due to the power of metabolomics. Along with identifying oncometabolites, such as (R)-2-hydroxyglutarate (R-2-HG), 3 metabolomic studies have revealed tumor-specific signatures, provided novel mechanistic insights into cancer phenotypes, and enhanced our understanding of drug action. 4 As reported in this issue of Neuro-Oncology, Björkblom et al 5 used multi-platform metabolomics to expand our knowledge related to glioma metabolism. The authors interrogated the characteristics of a large series of adult glial tumors (n= 224) using gas chromatography-and liquid chromatography mass spectrometry (GC-MS and LC-MS). Quantification of 1132 metabolic features, with 240 unique metabolites identified, was integrated with genetic, clinical, and pathological analyses, thereby offering a comprehensive view of the metabolic phenotypes for six WHO classified adult glioma subtypes.A key finding of the study is that isocitrate dehydrogenase (IDH)-wildtype tumors (n= 172) and IDH-mutated tumors (n= 52) had a significantly different metabolic profile, even if 2-HG, present in high levels in IDH-mutated tumors, was excluded from the analysis. While the result might not seem surprising, it has several interesting implications. Tumor metabolism has a cell-autonomous core, but it is also highly influenced by extrinsic factors and can, in turn, influence the microenvironment. Autonomous determinants include genetic aberrations and oncogene addiction, whereas environment-driven effects can be traced back to nutrient and oxygen availability and interactions with non-cancerous cells as well as with the extracellular matrix. 6 The fact that the WHO classified adult glioma subtypes have different metabolic profiles suggests robustness and specificity of the cellautonomous metabolic component for each subtype and confirms the potential of metabolic phenotypes as major