IF 2.1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
International Journal of General Medicine Pub Date : 2024-12-13 eCollection Date: 2024-01-01 DOI:10.2147/IJGM.S493488
Zhenxiang Zhao, Na Xing, Guozhu Sun
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引用次数: 0

摘要

目的: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讨。本研究旨在通过将孟德尔随机化(MR)分析与临床验证相结合来填补这一空白:分别从脑脊液(CSF)代谢物、血浆代谢物和 GBM 的全基因组关联研究(GWAS)中获取摘要数据。共有 338 种 CSF 代谢物和 1400 种血浆代谢物被用作暴露因子。同时,GBM 被指定为结果。为了研究潜在的关联性,我们进行了双样本双向磁共振研究。反方差加权(IVW)分析是作为因果关系估计进行的,同时还进行了一系列敏感性分析,以评估结果的稳健性。此外,还使用液相色谱-质谱法对临床血浆和脑脊液样本中的代谢物水平进行了定量分析,以验证研究结果:结果:磁共振分析确定了 8 种脑脊液代谢物和 6 种血浆代谢物与 GBM 密切相关。其中,脑脊液和血浆中7-α-羟基-3-氧代-4-胆甾烯酸盐(7-HOCA)水平的升高被认为会促进GBM的发生。在临床验证方面,与对照组相比,GBM 组脑脊液和血浆中的 7-HOCA 水平均显著升高:本研究全面分析了导致 GBM 的代谢因素。结论:本研究全面分析了导致 GBM 的代谢因素,发现了在 GBM 发病机制中起重要作用的特定代谢物,尤其是 7-HOCA,这提示了新的生物标记物和治疗靶点,为改进 GBM 的诊断和治疗提供了潜在的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of 7-HOCA as a Potential Biomarker in Glioblastoma: Evidence from Genome-Wide Association Study and Clinical Validation.

Purpose: 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.

Patients and methods: 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.

Results: 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.

Conclusion: 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.

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来源期刊
International Journal of General Medicine
International Journal of General Medicine Medicine-General Medicine
自引率
0.00%
发文量
1113
审稿时长
16 weeks
期刊介绍: The International Journal of General Medicine is an international, peer-reviewed, open access journal that focuses on general and internal medicine, pathogenesis, epidemiology, diagnosis, monitoring and treatment protocols. The journal is characterized by the rapid reporting of reviews, original research and clinical studies across all disease areas. A key focus of the journal is the elucidation of disease processes and management protocols resulting in improved outcomes for the patient. Patient perspectives such as satisfaction, quality of life, health literacy and communication and their role in developing new healthcare programs and optimizing clinical outcomes are major areas of interest for the journal. As of 1st April 2019, the International Journal of General Medicine will no longer consider meta-analyses for publication.
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