Zhao Zhenxiang, Xing Na, Sun Guozhu
Department of Neurosurgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China.
Department of Endocrinology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China.
Int J Gen Med. 2024 Dec 13;17:6185-6197. doi: 10.2147/IJGM.S493488. eCollection 2024.
Glioblastoma (GBM) is associated with metabolic disturbances, yet the relationships between metabolites with GBM have not been comprehensively explored. This study aims to fill this gap by integrating Mendelian randomization (MR) analysis with clinical validation.
Summary data from genome-wide association study (GWAS) of cerebrospinal fluid (CSF) metabolites, plasma metabolites, and GBM were obtained separately. A total of 338 CSF metabolites and 1400 plasma metabolites were utilized as exposures. Concurrently, GBM was designated as the outcome. A two-sample bidirectional MR study was conducted to investigate the potential association. The inverse variance weighted (IVW) analyses were conducted as causal estimates, accompanied by a series of sensitivity analyses to evaluate the robustness of the results. Additionally, metabolite levels in clinical plasma and CSF samples were quantified using liquid chromatography-mass spectrometry to validate the findings.
MR analysis identified eight CSF metabolites and six plasma metabolites that were closely associated with GBM. Among these, elevated levels of 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-HOCA) in both CSF and plasma were found to promote GBM. In terms of clinical validation, compared to the control group, 7-HOCA levels were significantly higher in both the CSF and plasma of GBM group.
This study provides a comprehensive analysis of the metabolic factors contributing to GBM. The identification of specific metabolites, particularly 7-HOCA, that have vital roles in GBM pathogenesis suggests new biomarkers and therapeutic targets, offering potential pathways for improved diagnosis and treatment of GBM.
胶质母细胞瘤（GBM）与代谢紊乱有关，但代谢物与GBM之间的关系尚未得到全面探索。本研究旨在通过整合孟德尔随机化（MR）分析与临床验证来填补这一空白。
分别获取脑脊液（CSF）代谢物、血浆代谢物和GBM的全基因组关联研究（GWAS）的汇总数据。总共338种CSF代谢物和1400种血浆代谢物被用作暴露因素。同时，将GBM指定为结局。进行了一项两样本双向MR研究以调查潜在关联。采用逆方差加权（IVW）分析作为因果估计，并进行了一系列敏感性分析以评估结果的稳健性。此外，使用液相色谱 - 质谱法定量临床血浆和CSF样本中的代谢物水平以验证研究结果。
MR分析确定了八种与GBM密切相关的CSF代谢物和六种血浆代谢物。其中，CSF和血浆中7-α-羟基-3-氧代-4-胆甾烯酸（7-HOCA）水平升高均被发现可促进GBM。在临床验证方面，与对照组相比，GBM组CSF和血浆中的7-HOCA水平均显著更高。
本研究对导致GBM的代谢因素进行了全面分析。鉴定出在GBM发病机制中起重要作用的特定代谢物，特别是7-HOCA，提示了新的生物标志物和治疗靶点，为改善GBM的诊断和治疗提供了潜在途径。
