Department of Chemistry, Umeå University, Linnaeus väg 10, 901 87, Umeå, Sweden.
Department of Clinical Science, Neurosciences, Umeå University, 901 85, Umeå, Sweden.
Sci Rep. 2024 Sep 5;14(1):20680. doi: 10.1038/s41598-024-71375-6.
Gliomas are highly complex and metabolically active brain tumors associated with poor prognosis. Recent reports have found altered levels of blood metabolites during early tumor development, suggesting that tumor development could be detected several years before clinical manifestation. In this study, we performed metabolite analyses of blood samples collected from healthy controls and future glioma patients, up to eight years before glioma diagnosis, and on the day of glioma surgery. We discovered that metabolites related to early glioma development were associated with an increased energy turnover, as highlighted by elevated levels of TCA-related metabolites such as fumarate, malate, lactate and pyruvate in pre-diagnostic cases. We also found that metabolites related to glioma progression at surgery were primarily high levels of amino acids and metabolites of amino acid catabolism, with elevated levels of 11 amino acids and two branched-chain alpha-ketoacids, ketoleucine and ketoisoleucine. High amino acid turnover in glioma tumor tissue is currently utilized for PET imaging, diagnosis and delineation of tumor margins. By examining blood-based metabolic progression patterns towards disease onset, we demonstrate that this high amino acid turnover is also detectable in a simple blood sample. These findings provide additional insight of metabolic alterations during glioma development and progression.
神经胶质瘤是高度复杂且代谢活跃的脑肿瘤，预后不良。最近的报告发现，在早期肿瘤发展过程中血液代谢物水平发生改变，这表明肿瘤的发展可能在临床症状出现前几年就被检测到。在这项研究中，我们对来自健康对照组和未来的神经胶质瘤患者的血液样本进行了代谢物分析，这些样本采集于神经胶质瘤诊断前长达八年的时间，并在神经胶质瘤手术当天进行了采集。我们发现，与早期神经胶质瘤发展相关的代谢物与能量代谢增加有关，这一点在预诊断病例中 TCA 相关代谢物（如富马酸、苹果酸、乳酸和丙酮酸）的水平升高中得到了体现。我们还发现，与手术时神经胶质瘤进展相关的代谢物主要是氨基酸水平升高和氨基酸分解代谢物升高，有 11 种氨基酸和两种支链α-酮酸（酮亮氨酸和酮异亮氨酸）水平升高。在神经胶质瘤肿瘤组织中，高氨基酸周转率目前用于 PET 成像、诊断和肿瘤边界的描绘。通过检查疾病发病前的基于血液的代谢进展模式，我们证明这种高氨基酸周转率在简单的血液样本中也能被检测到。这些发现为神经胶质瘤发展和进展过程中的代谢改变提供了更多的见解。
