Wen Jiayu, He Jian-Qing
Department of Respiratory and Critical Care Medicine, The Second People's Hospital of Meishan City, Renshou County, Meishan, China.
Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.
Discov Oncol. 2025 May 2;16(1):656. doi: 10.1007/s12672-025-02450-1.
The causative relationship between lung cancer subtypes and lipids is yet unknown. This research aims to elucidate the potential causative link connecting lipid levels to lung cancer subtypes, particularly focusing on non-small cell lung cancer (NSCLC), using the Mendelian randomization (MR) method and meta-analysis.
Summary statistics were obtained from genome-wide association study (GWAS) datasets. A comprehensive MR analysis was performed to explore the causal role of lipids in NSCLC subtypes. To ensure the reliability of the results, an external dataset was used for validation, and a meta-analysis was performed for further synthesis.
Two of the 179 lipids examined showed potential causal connection with lung adenocarcinoma (LUAD) and three with lung squamous cell carcinoma (LUSC). Specifically, phosphatidylcholine (PC) (16:0_20:4) and PC (18:0_20:4) might be connected to an elevated risk of LUSC, but PC (18:0_20:2) might be linked to a decreased risk. It was discovered that PC (16:1_20:4) and PC (18:0_20:4) might raise the risk for LUAD.
Complex lipid metabolic pathways, especially involving PC, are present in NSCLC, and distinct lipid isomers may influence various molecular subtypes in different ways.
肺癌亚型与血脂之间的因果关系尚不清楚。本研究旨在利用孟德尔随机化（MR）方法和荟萃分析，阐明血脂水平与肺癌亚型之间潜在的因果联系，尤其关注非小细胞肺癌（NSCLC）。
从全基因组关联研究（GWAS）数据集中获取汇总统计数据。进行了全面的MR分析，以探讨血脂在NSCLC亚型中的因果作用。为确保结果的可靠性，使用外部数据集进行验证，并进行荟萃分析以进一步综合分析。
在检测的179种血脂中，有两种显示出与肺腺癌（LUAD）存在潜在因果联系，三种与肺鳞状细胞癌（LUSC）存在潜在因果联系。具体而言，磷脂酰胆碱（PC）（16:0_20:4）和PC（18:0_20:4）可能与LUSC风险升高有关，但PC（18:0_20:2）可能与风险降低有关。研究发现，PC（16:1_20:4）和PC（18:0_20:4）可能会增加LUAD的风险。
NSCLC中存在复杂的脂质代谢途径，尤其是涉及PC的途径，不同的脂质异构体可能以不同方式影响各种分子亚型。
