Department of Neurosurgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde, Hunan 415003, People’s Republic of China.
Aging (Albany NY). 2024 May 10;16(9):8306-8319. doi: 10.18632/aging.205818.
Glioblastoma Multiforme (GBM) is one of the most aggressive and fatal brain cancers. The study of metabolites could be crucial for understanding GBM's biology and reveal new treatment strategies.
The GWAS data for GBM were sourced from the FinnGen database. A total of 1400 plasma metabolites were collected from the GWAS Catalog dataset. The cerebrospinal fluid (CSF) metabolites data were collected from subsets of participants in the WADRC and WRAP studies. We utilized the inverse variance weighting (IVW) method as the primary tool to explore the causal relationship between metabolites in plasma and CSF and glioblastoma, ensuring the exclusion of instances with horizontal pleiotropy. Additionally, four supplementary analytical methods were applied to reinforce our findings. Aberrant results were identified and omitted based on the outcomes of the leave-one-out sensitivity analysis. Conclusively, a reverse Mendelian Randomization analysis was also conducted to further substantiate our results.
The study identified 69 plasma metabolites associated with GBM. Of these, 40 metabolites demonstrated a significant positive causal relationship with GBM, while 29 exhibited a significant negative causal association. Notably, Trimethylamine N-oxide (TMAO) levels in plasma, not CSF, were found to be a significant exposure factor for GBM (OR = 3.1627, 95% CI = (1.6347, 6.1189), = 0.0006). The study did not find a reverse causal relationship between GBM and plasma TMAO levels.
This research has identified 69 plasma metabolites potentially associated with the incidence of GBM, among which TMAO stands out as a promising candidate for an early detectable biomarker for GBM.
多形性胶质母细胞瘤（GBM）是最具侵袭性和致命性的脑癌之一。代谢物的研究对于了解 GBM 的生物学特性并揭示新的治疗策略可能至关重要。
GBM 的 GWAS 数据来自 FinnGen 数据库。从 GWAS Catalog 数据集共收集了 1400 种血浆代谢物。脑脊液（CSF）代谢物数据来自 WADRC 和 WRAP 研究的参与者子集。我们使用逆方差加权（IVW）方法作为主要工具，探索血浆和 CSF 代谢物与胶质母细胞瘤之间的因果关系，确保排除水平多效性的实例。此外，还应用了四种补充分析方法来加强我们的发现。基于遗漏敏感性分析的结果，确定并省略了异常结果。最后，还进行了反向孟德尔随机化分析以进一步证实我们的结果。
该研究确定了 69 种与 GBM 相关的血浆代谢物。其中，40 种代谢物与 GBM 呈显著正因果关系，29 种代谢物与 GBM 呈显著负因果关系。值得注意的是，血浆而非 CSF 中的三甲胺 N-氧化物（TMAO）水平被发现是 GBM 的一个显著暴露因素（OR = 3.1627，95%CI =（1.6347，6.1189）， = 0.0006）。该研究未发现 GBM 与血浆 TMAO 水平之间的反向因果关系。
本研究确定了 69 种可能与 GBM 发病率相关的血浆代谢物，其中 TMAO 是 GBM 早期可检测生物标志物的一个有希望的候选物。
