Metabolomics Approach Reveals Important Glioblastoma Plasma Biomarkers for Tumor Biology.
Metabolomics Approach Reveals Important Glioblastoma Plasma Biomarkers for Tumor Biology.
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代谢组学方法揭示了肿瘤生物学的重要胶质母细胞瘤血浆生物标志物。
DOI：
10.3390/ijms24108813
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发表时间：
2023-05-16
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
胶质母细胞瘤（GB）是中枢神经系统最具侵袭性和最常见的原发性恶性肿瘤，即使在治疗后也与总体生存率低相关。为了更好地了解肿瘤生化改变并拓宽GB的潜在靶点，本研究旨在使用代谢组学分析来评估GB患者和健康个体之间的差异血浆生物标志物。通过非靶向代谢组学，使用电喷雾电离源和LTQ质谱仪直接进样分析两组的血浆样品。通过偏最小二乘判别和倍数变化分析选择GB生物标志物，并使用串联质谱法与计算机碎片化、代谢组学数据库咨询和文献检索进行鉴定。鉴定了7种GB生物标志物，其中一些是GB前所未有的生物标志物，包括N-乙酰脯氨酸（m/z 294）、5-羟甲基尿嘧啶（m/z 143）和N-酰基磷脂酰乙醇胺（m/z 982）。值得注意的是，还鉴别出了其他四种代谢物。阐明了所有七种代谢物在表观遗传调节、能量代谢、蛋白质催化或折叠过程以及激活细胞增殖和侵袭的信号通路中的作用。总的来说，这项研究的结果突出了新的分子靶点，以指导未来对GB的研究。这些分子靶点也可以进一步评估，以获得其作为外周血样本生物医学分析工具的潜力。
Glioblastoma (GB) is the most aggressive and frequent primary malignant tumor of the central nervous system and is associated with poor overall survival even after treatment. To better understand tumor biochemical alterations and broaden the potential targets of GB, this study aimed to evaluate differential plasma biomarkers between GB patients and healthy individuals using metabolomics analysis. Plasma samples from both groups were analyzed via untargeted metabolomics using direct injection with an electrospray ionization source and an LTQ mass spectrometer. GB biomarkers were selected via Partial Least Squares Discriminant and Fold-Change analyses and were identified using tandem mass spectrometry with in silico fragmentation, consultation of metabolomics databases, and a literature search. Seven GB biomarkers were identified, some of which were unprecedented biomarkers for GB, including arginylproline (m/z 294), 5-hydroxymethyluracil (m/z 143), and N-acylphosphatidylethanolamine (m/z 982). Notably, four other metabolites were identified. The roles of all seven metabolites in epigenetic modulation, energy metabolism, protein catabolism or folding processes, and signaling pathways that activate cell proliferation and invasion were elucidated. Overall, the findings of this study highlight new molecular targets to guide future investigations on GB. These molecular targets can also be further evaluated to derive their potential as biomedical analytical tools for peripheral blood samples.
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