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Indirect Roles of Immunophenotypes in the Association Between Glycerophospholipid Metabolism and Endometrial Cancer
Yichen Shen1, Yijing Yan2, Peizhe Lin3
1School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.
International Journal of Women'S Health
|April 21, 2026
Summary
Altered lipid metabolism, specifically glycerophospholipid metabolism, is linked to endometrial cancer (EC) risk. Certain metabolites influence EC risk through indirect pathways involving immune cells, offering new diagnostic and therapeutic targets.
Area of Science:
- Oncology
- Metabolomics
- Immunology
Background:
- Endometrial cancer (EC) incidence is rising globally.
- Lipid metabolic alterations in serum are increasingly linked to cancer progression.
Purpose of the Study:
- To investigate potential causal associations between glycerophospholipid metabolism and EC risk.
- To explore indirect roles of immunophenotypes in these associations.
Main Methods:
- Two-step, two-sample Mendelian Randomization (MR) methodology.
- Utilized data from GWAS Catalog and EC Association Consortium.
- Employed multiple MR methods (Inverse Variance Weighted, MR-Egger, etc.) and sensitivity analyses.
Main Results:
- Three genetically predicted metabolites associated with EC risk.
- 1-(1-enyl-palmitoyl)-GPC (p-16:0) and 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1) decreased EC risk.
- Eicosenedioate (C20:1-DC) increased EC risk, mediated by CD38 on PB/PC cells.
Conclusions:
- Provides genetic evidence for causal links between glycerophospholipid metabolism and EC.
- Identifies potential indirect pathways involving immunophenotypes (e.g., B cells, T cells).
- Suggests novel avenues for EC diagnosis and therapy.
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