Lou Yaochen, Jiang Feng, Guan Jun
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Front Oncol. 2024 Oct 18;14:1436955. doi: 10.3389/fonc.2024.1436955. eCollection 2024.
This study aimed to explore the potential effects between various human plasma lipidomes and endometrioid endometrial cancer (EEC) by using Mendelian randomization (MR) methods.
This study designated a total of 179 human plasma lipidomes from the genome-wide association study (GWAS) database as the exposure variable. An EEC-related dataset from the GWAS (GCST006465) served as the outcome variable. MR analyses used the inverse variance-weighted method (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods for regression calculations, accounting for possible biases induced by linkage disequilibrium and weak instrument variables. Any lipidomes failing to pass heterogeneity and horizontal pleiotropy tests were deemed to lack significant causal impact on the outcome.
The results of IVW analysis disclosed that a variety of human plasma lipidomes (n = 15) exhibited a significant causal effect on EEC (p < 0.05). A subset of these lipidomes (n = 13) passed heterogeneity and horizontal pleiotropy tests, which demonstrated consistent and viable causal effects (p < 0.05) including glycerophospholipids, glycerolipids, and sterols. Specifically, phosphatidylcholine (odds ratio [OR]: 1.065-1.129, p < 0.05) exhibited a significant positive causal effect on the occurrence of EEC. Conversely, sterol ester (OR = 0.936, p = 0.007), diacylglycerol (OR = 0.914, p = 0.036), phosphatidylcholine (OR: 0.903-0.927, p < 0.05), phosphatidylethanolamine (OR = 0.907, p = 0.046) and triacylglycerol (OR: 0.880-0.924, p < 0.05) showed a notable negative causal association with EEC, suggesting their inhibitory effects on the EEC occurrence.
The study revealed that human plasma lipidomes have complex impacts on EEC through Mendelian randomization. This indicated that the diversity of structural changes in lipidomes could show different effects on subtypes and then affect EEC occurrence. Although these lipids had the potential to be promising biomarkers, they needed to be further clinically validated nevertheless.
本研究旨在采用孟德尔随机化（MR）方法探讨各种人类血浆脂质组与子宫内膜样腺癌（EEC）之间的潜在影响。
本研究将来自全基因组关联研究（GWAS）数据库的总共179种人类血浆脂质组指定为暴露变量。来自GWAS的EEC相关数据集（GCST006465）用作结果变量。MR分析使用逆方差加权法（IVW）、MR-Egger法、加权中位数法、简单模式法和加权模式法进行回归计算，考虑了连锁不平衡和弱工具变量引起的可能偏差。任何未通过异质性和水平多效性检验的脂质组被认为对结果缺乏显著因果影响。
IVW分析结果显示，多种人类血浆脂质组（n = 15）对EEC表现出显著因果效应（p < 0.05）。这些脂质组中的一部分（n = 13）通过了异质性和水平多效性检验，显示出一致且可行的因果效应（p < 0.05），包括甘油磷脂、甘油脂和甾醇。具体而言，磷脂酰胆碱（优势比[OR]：1.065 - 1.129，p < 0.05）对EEC的发生表现出显著的正向因果效应。相反，甾醇酯（OR = 0.936，p = 0.007）、二酰基甘油（OR = 0.914，p = 0.036）、磷脂酰胆碱（OR：0.903 - 0.927，p < 0.05）、磷脂酰乙醇胺（OR = 0.907，p = 0.046）和三酰基甘油（OR：0.880 - 0.924，p < 0.05）与EEC呈现出显著的负向因果关联，表明它们对EEC发生具有抑制作用。
该研究表明，人类血浆脂质组通过孟德尔随机化对EEC具有复杂影响。这表明脂质组结构变化的多样性可能对亚型表现出不同影响，进而影响EEC的发生。尽管这些脂质有潜力成为有前景的生物标志物，但仍需要进一步的临床验证。
