LC–MS-Based Urine Metabolomics Analysis for the Diagnosis and Monitoring of Medulloblastoma

• DOI: 10.3389/fonc.2022.949513
• Publication Date: 2022-07-22T05:39:06Z
• Authors: Xiaoyan Liu; Jing Li; Xiaolei Hao; Haidan Sun; Yang Zhang; Liwei Zhang; Lulu Jia; Yongji Tian; Wei Sun
• Keywords: cortolone; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; medulloblastoma; metabolomics; urine; 6. Clean water; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Oncology; biomarker; tetrahydrocortisone; RC254-282

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.