Department of Neurosurgery and Neuro-Oncology, Medical University of Lodz, Barlicki University Hospital, Kopcinskiego St. 22, 90-153, Lodz, Poland.
Department of Structural Biology, Medical University of Lodz, Lodz, Poland.
Amino Acids. 2021 Jan;53(1):119-132. doi: 10.1007/s00726-020-02931-3. Epub 2021 Jan 4.
Glioblastoma (GB) is the most common primary brain tumour in adults. The lack of molecular biomarker, non-specific symptoms and fast growth rate often result in a significant delay in diagnosis. Despite multimodal treatment, the prognosis remains poor. Here, we verified the hypothesis that amino acids (AA) regulating the critical metabolic pathways necessary for maintenance, growth, reproduction, and immunity of an organism, may constitute a favourable target in GB biomarker research. We measured the plasma amino acids levels in 18 GB patients and 15 controls and performed the quantitative and qualitative metabolomic analysis of free AA applying high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). We present both the raw data and the results of our statistical analysis. The majority of AA were lowered in the study group in comparison to the control group. Five of these (arginine, glutamic acid, glutamine, glycine, and histidine) differed significantly (all p < 10 and AUC > 0.9). Plasma levels of leucine and phenylalanine decreased in the case of GB with lost alpha-thalassemia/mental retardation X-linked (ATRX) expression on immunohistochemistry (p = 0.003 and 0.045, respectively). We demonstrated for the first time that certain plasma-free AA levels of GB patients were significantly different from those in healthy volunteers. Target profiling of plasma-free AA, identified utilizing LC-QTOF-MS, may present prognostic value by indicating GB patients with lost ATRX expression. The on-going quest for glioma biomarkers still aims to determine the detailed metabolic profile and evaluate its impact on therapy and prognosis.
胶质母细胞瘤(GB)是成人中最常见的原发性脑肿瘤。由于缺乏分子生物标志物、非特异性症状和快速的生长速度,导致诊断常常出现明显的延迟。尽管采用了多模式治疗,但预后仍然较差。在这里,我们验证了这样一个假设,即氨基酸(AA)调节维持、生长、繁殖和免疫所必需的关键代谢途径,可能构成 GB 生物标志物研究的一个有利目标。我们测量了 18 名 GB 患者和 15 名对照者的血浆氨基酸水平,并应用高效液相色谱四极杆飞行时间质谱(LC-QTOF-MS)对游离 AA 进行了定量和定性代谢组学分析。我们提供了原始数据和统计分析结果。与对照组相比,研究组中的大多数 AA 水平降低。其中 5 种(精氨酸、谷氨酸、谷氨酰胺、甘氨酸和组氨酸)差异显著(均 p<10,AUC>0.9)。在免疫组化显示失去 X 连锁的 alpha-地中海贫血/智力低下(ATRX)表达的情况下,GB 患者的血浆亮氨酸和苯丙氨酸水平降低(分别为 p=0.003 和 0.045)。我们首次证明,某些 GB 患者的血浆游离 AA 水平与健康志愿者明显不同。利用 LC-QTOF-MS 进行的游离 AA 靶向分析可能具有预后价值,表明失去 ATRX 表达的 GB 患者。寻找神经胶质瘤生物标志物的研究仍旨在确定详细的代谢谱,并评估其对治疗和预后的影响。