Pan Hongyu, Hu Jinyu, Gong Shanshan, Fei Yuchang
Department of Traditional Chinese Medicine, Shangyu People's Hospital of Shaoxing, Shaoxing University, Shaoxing, Zhejiang, China.
Department of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Discov Oncol. 2025 May 23;16(1):868. doi: 10.1007/s12672-025-02704-y.
Clinical observational studies have highlighted differences in plasma lipid profiles between lung carcinoma patients and healthy individuals. However, the causal relationship underlying these differences remains unclear. This study aims to investigate the bidirectional causal relationship between 179 plasma lipids and lung carcinoma.
A bivariate two-sample Mendelian randomization (MR) study was conducted using data from public genome-wide association studies (GWAS). The primary analytical technique employed was the inverse variance weighting method (IVW), with MR-Egger, weighted-median, and weighted mode as supplementary methods. Sensitivity analyses including Cochran's Q test and MR-Egger intercept test were performed to ensure the robustness of the results.
Mendelian randomization analysis revealed positive associations between levels of certain plasma lipidome-Sterol ester 27:1/20:5 levels (OR 1.162, 95% confidence interval (CI) 1.077-1254, P 1.15e), Phosphatidylcholine (PC) 20:4_0:0 levels (OR 1.112, 95%CI 1.051-1.176, P 2.33e), PC 17:0_20:4 levels (OR 1.108, 95%CI 1.051-1.167, P 1.33e, PC 18:0_20:4 levels (OR 1.094, 95%CI 1.046-1.144, P 8.08e), PC O-16:0:4 levels (OR 1.180, 95%CI 1.089-1.277, P4.61e), PC O-16:1_20:4 levels (OR 1.155, 95%CI 1.077-1.239, P 5.00e)-with the risk of lung carcinoma. Conversely, PC 15:0_18:2 levels (OR 0.823, 95%CI 0.760-0.892, P1.95e), PC 16:0_18:2 levels (OR 0.863, 95%CI 0.801-0.931, P 1.28e), PC 16:1_18:2 levels (OR 0.856, 95%CI 0.791-0.926, P 1.13e), PC 18:1_18:2 levels (OR 0.847, 95%CI 0.77-0.911, P 9.15e) were inversely associated with the risk of lung carcinoma. Reverse Mendelian randomization analysis indicated that lung carcinoma did not have a significant causal effect on the 179 plasma lipids.
Our study reveals the causal relationship between plasma lipidome and lung cancer, provides preliminary genetic evidence, and provides a new idea for understanding the pathogenesis of lung cancer and finding promising therapeutic targets.
临床观察性研究突显了肺癌患者与健康个体之间血浆脂质谱的差异。然而，这些差异背后的因果关系仍不明确。本研究旨在探究179种血浆脂质与肺癌之间的双向因果关系。
使用来自公共全基因组关联研究（GWAS）的数据进行双变量两样本孟德尔随机化（MR）研究。采用的主要分析技术是逆方差加权法（IVW），以MR-Egger、加权中位数和加权模式作为补充方法。进行了包括 Cochr an's Q检验和MR-Egger截距检验在内的敏感性分析，以确保结果的稳健性。
孟德尔随机化分析显示，某些血浆脂质组水平与肺癌风险之间存在正相关，包括甾醇酯27:1/20:5水平（比值比[OR] 1.162，95%置信区间[CI] 1.077 - 1.254，P 1.15e）、磷脂酰胆碱（PC）20:4_0:0水平（OR 1.112，95%CI 1.051 - 1.176，P 2.33e）、PC 17:0_20:4水平（OR 1.108，95%CI 1.051 - 1.167，P 1.33e）、PC 18:0_20:4水平（OR 1.094，95%CI 1.046 - 1.144，P 8.08e）、PC O-16:0:4水平（OR 1.180，95%CI 1.089 - 1.277，P 4.61e）、PC O-16:1_20:4水平（OR 1.155，95%CI 1.077 - 1.239，P 5.00e）。相反，PC 15:0_18:2水平（OR 0.823，95%CI 0.760 - 0.892，P 1.95e）、PC 16:0_18:2水平（OR 0.863，95%CI 0.801 - 0.931，P 1.28e）、PC 16:1_18:2水平（OR 0.856，95%CI 0.791 - 0.926，P 1.13e）、PC 18:1_18:2水平（OR 0.847，95%CI 0.77 - 0.911，P 9.15e）与肺癌风险呈负相关。反向孟德尔随机化分析表明，肺癌对这179种血浆脂质没有显著的因果效应。
我们的研究揭示了血浆脂质组与肺癌之间的因果关系，提供了初步的遗传证据，并为理解肺癌的发病机制和寻找有前景的治疗靶点提供了新思路。
