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中国药学(英文版) ›› 2026, Vol. 35 ›› Issue (6): 560-573.DOI: 10.5246/jcps.2026.06.040

• 【研究论文】 • 上一篇    下一篇

免疫细胞在介导脂质组对ER+乳腺癌风险及其预后的作用: 一项孟德尔随机化研究

陈芬燕1,#, 胡聪婷1,#, 彭萍萍2,#, 蔡梓铭2, 刘苏燕3, 刘佳2, 蔡加琴1, 魏晓霞1,*(), 孙红1,*()   

  1. 1. 福建医科大学省立临床医学院、福建省立医院、福州大学附属省立医院 药学部,福建 福州 350001
    2. 福建医科大学药学院;福建省立医院、福建医科大学省立临床医学院、福州大学附属省立医院,福建 福州 350001
    3. 福建中医药大学药学院;福建省立医院、福建医科大学省立临床医学院、福州大学附属省立医院,福建 福州 350001
  • 收稿日期:2026-03-10 修回日期:2026-04-05 接受日期:2026-04-21 出版日期:2026-07-05 发布日期:2026-07-05
  • 通讯作者: 魏晓霞, 孙红

The role of immune cells in mediating the effects and prognosis of lipidome in ER+ breast cancer: A mendelian randomization study

Fenyan Chen1,#, Congting Hu1,#, Pingping Peng2,#, Ziming Cai2, Suyan Liu3, Jia Liu2, Jiaqin Cai1, Xiaoxia Wei1,*(), Hong Sun1,*()   

  1. 1. Department of Pharmacy, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, Fujian, China
    2. School of Pharmacy, Fujian Medical University, School of Pharmacy, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, Fujian, China
    3. School of Pharmacy, Fujian University of Traditional Chinese Medicine; Department of Pharmacy, Fujian Provincial Hospital, Fuzhou 350001, Fujian, China
  • Received:2026-03-10 Revised:2026-04-05 Accepted:2026-04-21 Online:2026-07-05 Published:2026-07-05
  • Contact: Xiaoxia Wei, Hong Sun
  • About author:

    # These authors contributed equally to this work.

  • Supported by:
    The Natural Science Foundation of Fujian, China (Grant No. 2022J011004), Fujian Provincial Joint Funding Project of Scientific and Technological Innovation (Grant No. 2023Y9298), and Fujian Provincial Health Technology Project (Grant No. 2022CXB001).

摘要:

既往研究表明,脂质组与免疫细胞在雌激素受体阳性(ER+)乳腺癌(BC)的发展中可能存在关联,但脂质的确切因果作用及其是否通过免疫细胞介导仍不完全清楚。为填补这一知识空白,本研究利用涵盖179种脂质物种的大规模全基因组关联研究(GWAS)数据,采用双样本孟德尔随机化(TSMR)作为主要分析框架,探讨不同分子脂质亚型对ER+BC风险以及短期(5年)和长期(15年)生存率的因果影响。研究进一步使用贝叶斯加权孟德尔随机化(BWMR)方法对主要因果估计进行验证,并进行了全面的敏感性分析(包括异质性和水平多效性评估),以严格确保结果的稳健性。结果表明,特定脂质类别——尤其是二酰基甘油、磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰肌醇和三酰甘油——对ER+BC的易感性和患者生存结局均具有显著的因果影响。此外,分析确定了29种与预后相关的免疫细胞表型,其中五种被显著识别为脂质组影响ER+BC生存的生物通路中的潜在关键介质。本研究提供了坚实的遗传学证据,支持脂质组与ER+BC的发病机制和进展之间存在因果关系,且这一关系似乎部分由特定免疫细胞群体介导。

关键词: ER+BC, 脂质组, 免疫细胞, 孟德尔随机化

Abstract:

Previous studies have suggested a potential interplay between the lipidome and immune cell dynamics in the development of estrogen receptor–positive (ER+) breast cancer (BC); however, the causal contribution of specific lipid species and their potential mediation through immune cells remain poorly defined. To address this gap, the present study leveraged large-scale genome-wide association study (GWAS) data covering 179 lipid species. Two-sample Mendelian randomization (TSMR) was employed as the primary analytical framework to systematically evaluate the causal effects of diverse molecular lipid subtypes on ER+BC risk, as well as on short-term (5-year) and long-term (15-year) survival outcomes. The robustness of the primary causal estimates was further examined using Bayesian weighted Mendelian randomization (BWMR), alongside comprehensive sensitivity analyses, including formal assessments of heterogeneity and horizontal pleiotropy. Our analyses revealed that several lipid classes, most notably diacylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and triacylglycerol, exerted significant causal effects on both ER+BC susceptibility and patient survival. In addition, 29 immune cell phenotypes were identified as being associated with prognosis, among which five emerged as potential key mediators linking lipid metabolism to ER+BC survival. Collectively, these findings provided robust genetic evidence supporting a causal role of the lipidome in the pathogenesis and progression of ER+BC, with this effect appearing to be partially mediated by specific immune cell populations.

Key words: ER+BC, Lipidome, Immune cell, Mendelian randomization

Supporting: /attached/file/20260710/20260710002531_646.pdf