Gu Shanshan, Wang Xu, Yang Hongxia, Wang Yaxuan, Yan Congya, Lin Xiaoting, Liu Peng, Liu Lu, Meng Li, Qi Guoyan
Department of Oncology, Hebei Medical University, Shijiazhuang, China.
Center of Treatment of Myasthenia Gravis, People's Hospital of Shijiazhuang Affiliated to Hebei Medical University, Shijiazhuang, China.
Discov Oncol. 2025 May 26;16(1):926. doi: 10.1007/s12672-025-02700-2.
This study aims to screen and identify metabolic biomarkers and targets for methylprednisolone treatment of thymoma with myasthenia gravis (MG) through metabolomics and network pharmacology analysis, thereby improving guidance for clinical medication and treatment.
Serum from 15 patients with thymoma accompanied by severe MG was collected. Changes in serum metabolite levels before and after methylprednisolone treatment were determined using liquid chromatography-mass spectrometry (LC-MS). The raw mass spectrometry fragment information obtained was integrated and interpreted using the metabolomics data analysis software Progenesis QI v2.3. Differential metabolites were screened and identified using univariate and multivariate statistical analysis methods. Subsequently, potential targets of methylprednisolone treatment were identified through network pharmacology, and the mechanism of action of methylprednisolone in treating thymoma with MG was explored in conjunction with metabolomics. Finally, key targets and the upstream synthetic enzymes of critical metabolites identified were validated using Enzyme-Linked Immunosorbent Assay (ELISA).
A total of 148 differential metabolites were identified in the metabolomics study, among which key metabolites ceramide (Cer) and sphingomyelin (SM) play a significant role in cell immune regulation, inflammatory response, and tumor control. Network pharmacology analysis revealed that tumor necrosis factor (TNF) could serve as a potential target for methylprednisolone treatment of thymoma with MG. ELISA validation results showed that the key target TNF and the upstream synthetic enzymes of the key metabolites SM and Cer were all downregulated after methylprednisolone treatment, with the differences being statistically significant (P < 0.05).
Our Study reveals that TNF could serve as a potential target for methylprednisolone treatment of Thymoma-associated MG, and Cer and SM could act as potential metabolic biomarkers to assess its treatment efficacy.
本研究旨在通过代谢组学和网络药理学分析，筛选并鉴定甲基强的松龙治疗重症肌无力（MG）合并胸腺瘤的代谢生物标志物和靶点，从而为临床用药和治疗提供指导。
收集15例重症MG合并胸腺瘤患者的血清。采用液相色谱 - 质谱联用（LC - MS）法测定甲基强的松龙治疗前后血清代谢物水平的变化。使用代谢组学数据分析软件Progenesis QI v2.3对获得的原始质谱碎片信息进行整合和解读。采用单变量和多变量统计分析方法筛选和鉴定差异代谢物。随后，通过网络药理学鉴定甲基强的松龙治疗的潜在靶点，并结合代谢组学探讨甲基强的松龙治疗MG合并胸腺瘤的作用机制。最后，使用酶联免疫吸附测定（ELISA）对鉴定出的关键靶点和关键代谢物的上游合成酶进行验证。
代谢组学研究共鉴定出148种差异代谢物，其中关键代谢物神经酰胺（Cer）和鞘磷脂（SM）在细胞免疫调节、炎症反应和肿瘤控制中起重要作用。网络药理学分析表明，肿瘤坏死因子（TNF）可作为甲基强的松龙治疗MG合并胸腺瘤的潜在靶点。ELISA验证结果显示，甲基强的松龙治疗后关键靶点TNF以及关键代谢物SM和Cer的上游合成酶均下调，差异具有统计学意义（P < 0.05）。
我们的研究表明，TNF可作为甲基强的松龙治疗胸腺瘤相关MG的潜在靶点，Cer和SM可作为评估其治疗效果的潜在代谢生物标志物。
