Wang Peng, Zhang Xin, Xiao Boan, Ouyang Jiecai, Zhang Jingjing, Peng Xiaobin
The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China.
Front Oncol. 2024 Sep 2;14:1428025. doi: 10.3389/fonc.2024.1428025. eCollection 2024.
The causal relationship and mechanisms between lipids and glioblastoma (GBM) remain unclear. This study aims to investigate the independent causal relationship between liposomal phosphatidylcholine 16:0_22:6 (PC16) and GBM, and to identify the potential mediating role of the inflammatory factor-fibroblast growth factor 21(FGF21).
Utilizing summary statistics from genome-wide association studies (GWAS) of lipids (179 types in 7174 Finnish individuals), GBM (243 cases and 287137 controls), and inflammatory factors (91 types in 14824 European individuals), a two-sample Mendelian Randomization (MR) approach was employed to establish the causal link between liposomal PC16 and GBM. Additionally, a two-step MR method was used to quantify the proportion of the causal effect of PC16 on GBM that is mediated by the inflammatory factor FGF21.
MR analyses revealed a strong causal relationship between PC16 and GBM (OR=1.72, 95% CI: 1.11-2.68, P=0.016), but no reverse causality was observed from GBM to PC16 (OR=1.01, 95% CI: 0.99-1.02, P=0.38). Mediation analysis showed a strong causal relationship between PC16 and the FGF21 (OR = 0.94, 95% CI: 0.89-0.99, P=0.018) as well as between FGF21 and GBM (OR = 0.42, 95% CI: 0.25-0.71, P=0.001), with the mediation effect accounting for 9.78% of the total effect. This suggests that the causal relationship between PC16 and GBM is likely mediated by the intermediary factor FGF21. No evidence of pleiotropy was found in the sensitivity analysis of these positive results.
In summary, the findings of this study suggest that liposomal PC16 may increase the risk of GBM occurrence, and FGF21 may play a significant mediating role in this causal relationship.
脂质与胶质母细胞瘤（GBM）之间的因果关系及机制仍不明确。本研究旨在探讨脂质体磷脂酰胆碱16:0_22:6（PC16）与GBM之间的独立因果关系，并确定炎症因子成纤维细胞生长因子21（FGF21）的潜在中介作用。
利用脂质（7174名芬兰个体中的179种类型）、GBM（243例病例和287137名对照）以及炎症因子（14824名欧洲个体中的91种类型）的全基因组关联研究（GWAS）的汇总统计数据，采用两样本孟德尔随机化（MR）方法建立脂质体PC16与GBM之间的因果联系。此外，使用两步MR方法量化PC16对GBM的因果效应中由炎症因子FGF21介导的比例。
MR分析显示PC16与GBM之间存在强因果关系（OR=1.72，95%CI：1.11-2.68，P=0.016），但未观察到从GBM到PC16的反向因果关系（OR=1.01，95%CI：0.99-1.02，P=0.38）。中介分析显示PC16与FGF21之间存在强因果关系（OR = 0.94，95%CI：0.89-0.99，P=0.018）以及FGF21与GBM之间存在强因果关系（OR = 0.42，95%CI：0.25-0.71，P=0.001），中介效应占总效应的9.78%。这表明PC16与GBM之间的因果关系可能由中介因子FGF21介导。在对这些阳性结果的敏感性分析中未发现多效性证据。
总之，本研究结果表明脂质体PC16可能增加GBM发生的风险，并且FGF21可能在这种因果关系中起重要的中介作用。
