Liu Xiaoyan, Li Jing, Hao Xiaolei, Sun Haidan, Zhang Yang, Zhang Liwei, Jia Lulu, Tian Yongji, Sun Wei
Core Instrument Facility, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
Department of Neurosurgery, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Front Oncol. 2022 Jul 22;12:949513. doi: 10.3389/fonc.2022.949513. eCollection 2022.
Medulloblastoma (MB) is the most common type of brain cancer in pediatric patients. Body fluid biomarkers will be helpful for clinical diagnosis and treatment. In this study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was used to identify specific urine metabolites of MB in a cohort, including 118 healthy controls, 111 MB patients, 31 patients with malignant brain cancer, 51 patients with benign brain disease, 29 MB patients 1 week postsurgery and 80 MB patients 1 month postsurgery. The results showed an apparent separation for MB vs. healthy controls, MB vs. benign brain diseases, and MB vs. other malignant brain tumors, with AUCs values of 0.947/0.906, 0.900/0.873, and 0.842/0.885, respectively, in the discovery/validation group. Among all differentially identified metabolites, 4 metabolites (tetrahydrocortisone, cortolone, urothion and 20-oxo-leukotriene E4) were specific to MB. The analysis of these 4 metabolites in pre- and postoperative MB urine samples showed that their levels returned to a healthy state after the operation (especially after one month), showing the potential specificity of these metabolites for MB. Finally, the combination of two metabolites, tetrahydrocortisone and cortolone, showed diagnostic accuracy for distinguishing MB from non-MB, with an AUC value of 0.851. Our data showed that urine metabolomics might be used for MB diagnosis and monitoring.
髓母细胞瘤（MB）是儿科患者中最常见的脑癌类型。体液生物标志物将有助于临床诊断和治疗。在本研究中，基于液相色谱 - 质谱联用（LC - MS）的代谢组学被用于在一个队列中鉴定MB的特定尿液代谢物，该队列包括118名健康对照、111名MB患者、31名恶性脑癌患者、51名良性脑病患者、29名术后1周的MB患者和80名术后1个月的MB患者。结果显示，在发现/验证组中，MB与健康对照、MB与良性脑病以及MB与其他恶性脑肿瘤之间存在明显分离，AUC值分别为0.947/0.906、0.900/0.873和0.842/0.885。在所有差异鉴定的代谢物中，有4种代谢物（四氢可的松、皮质酮、尿硫醇和20 - 氧代 - 白三烯E4）对MB具有特异性。对术前和术后MB尿液样本中这4种代谢物的分析表明，术后（尤其是1个月后）它们的水平恢复到健康状态，显示出这些代谢物对MB的潜在特异性。最后，四氢可的松和皮质酮这两种代谢物的组合在区分MB与非MB方面显示出诊断准确性，AUC值为0.851。我们的数据表明，尿液代谢组学可能用于MB的诊断和监测。
