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Plasma amino acids indicate glioblastoma with ATRX loss
Amino Acids ( IF 3.0 ) Pub Date : 2021-01-04 , DOI: 10.1007/s00726-020-02931-3
Ernest Jan Bobeff 1 , Dorota Szczesna 2 , Michał Bieńkowski 3 , Karolina Janczar 4 , Malgorzata Chmielewska-Kassassir 2 , Karol Wiśniewski 1 , Wielisław Papierz 5 , Lucyna Alicja Wozniak 2 , Dariusz Jan Jaskólski 1
Affiliation  

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 < 10–5 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.



中文翻译:

血浆氨基酸表明具有 ATRX 损失的胶质母细胞瘤

胶质母细胞瘤 (GB) 是成人中最常见的原发性脑肿瘤。分子生物标志物的缺乏、非特异性症状和快速增长往往导致诊断的显着延迟。尽管进行了多模式治疗,但预后仍然很差。在这里,我们验证了氨基酸 (AA) 调节生物体维持、生长、繁殖和免疫所需的关键代谢途径的假设,可能构成 GB 生物标志物研究的有利目标。我们测量了 18 名 GB 患者和 15 名对照的血浆氨基酸水平,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的结果。与对照组相比,研究组的大部分 AA 降低。其中五个(精氨酸、谷氨酸、谷氨酰胺、甘氨酸和组氨酸)差异显着(所有p  < 10 –5和 AUC > 0.9)。GB 的血浆亮氨酸和苯丙氨酸水平降低,免疫组化显示 α-地中海贫血/智力低下 X 连锁 (ATRX) 表达缺失( 分别为p = 0.003 和 0.045)。我们首次证明 GB 患者的某些无血浆 AA 水平与健康志愿者显着不同。使用 LC-QTOF-MS 鉴定的无血浆 AA 的靶标分析可能通过指示失去 ATRX 表达的 GB 患者来提供预后价值。对胶质瘤生物标志物的持续探索仍旨在确定详细的代谢特征并评估其对治疗和预后的影响。

更新日期:2021-01-05
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