Immune cells mediate the association between the plasma lipidome and pancreatic cancer: a Mendelian randomization analysis
Abstract The plasma liposome was associated with pancreatic cancer (PC) but the specific mechanism was still unclear. We aim to investigate the relationship between the plasma lipidome and PC risk, as well as the mediating roles of immune cells. Based on summary genome-wide association study (GWAS)...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-05898-x |
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| author | Chunhong Ma Dandan Liu Changchun Ye Zilu Chen Ranran Kong Jianzhong Li Xuejun Sun Zhengshui Xu |
| author_facet | Chunhong Ma Dandan Liu Changchun Ye Zilu Chen Ranran Kong Jianzhong Li Xuejun Sun Zhengshui Xu |
| author_sort | Chunhong Ma |
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| description | Abstract The plasma liposome was associated with pancreatic cancer (PC) but the specific mechanism was still unclear. We aim to investigate the relationship between the plasma lipidome and PC risk, as well as the mediating roles of immune cells. Based on summary genome-wide association study (GWAS) statistics of 179 plasma lipidomes, 791 immune cells, and PC patients of European ancestry, two-sample MR analysis was utilized to identify the relationship between the lipidome and PC. Then, the two-step MR method was used to investigate the mediating role of immune cells and calculate the mediation effects. Sensitivity analysis was employed to evaluate the reliability of the findings. According to the inverse variance weighted (IVW) results, higher phosphatidylcholine (O−16:0_20:4) (P = 0.0248), phosphatidylinositol (18:0_20:4) (P = 0.0268), triacylglycerol (54:6) (P = 0.0415), and sterol ester (27:1/15:0) (P = 0.0138) levels reduced PC risk, while phosphatidylcholine (16:0_20:3) (P = 0.0295) and higher sphingomyelin (d40:1) (P = 0.0217) levels increased PC risk. Additionally, 22 immune cells had an effect on PC. Among those, only CD4 Regulatory T (Treg) AC cells played a mediating role between phosphatidylinositol (18:0_20:4) and PC (proportion mediated: 10.5%). No significant heterogeneity or pleiotropy was observed. The present study showed that PC risk was impacted by phosphatidylcholine, phosphatidylinositol, triacylglycerol, sterol ester, and sphingomyelin levels. The causal relationship between phosphatidylinositol (18:0_20:4) and PC was mediated by CD4 Treg AC cells, which provides insight for immunotherapy. |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-6dc896a0c3034bcbb67bd8f6ac22f0aa2025-08-20T04:02:46ZengNature PortfolioScientific Reports2045-23222025-07-011511710.1038/s41598-025-05898-xImmune cells mediate the association between the plasma lipidome and pancreatic cancer: a Mendelian randomization analysisChunhong Ma0Dandan Liu1Changchun Ye2Zilu Chen3Ranran Kong4Jianzhong Li5Xuejun Sun6Zhengshui Xu7Department of Thoracic Surgery, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Thoracic Surgery, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Thoracic Surgery, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Thoracic Surgery, The Second Affiliated Hospital of Xi’an Jiaotong UniversityAbstract The plasma liposome was associated with pancreatic cancer (PC) but the specific mechanism was still unclear. We aim to investigate the relationship between the plasma lipidome and PC risk, as well as the mediating roles of immune cells. Based on summary genome-wide association study (GWAS) statistics of 179 plasma lipidomes, 791 immune cells, and PC patients of European ancestry, two-sample MR analysis was utilized to identify the relationship between the lipidome and PC. Then, the two-step MR method was used to investigate the mediating role of immune cells and calculate the mediation effects. Sensitivity analysis was employed to evaluate the reliability of the findings. According to the inverse variance weighted (IVW) results, higher phosphatidylcholine (O−16:0_20:4) (P = 0.0248), phosphatidylinositol (18:0_20:4) (P = 0.0268), triacylglycerol (54:6) (P = 0.0415), and sterol ester (27:1/15:0) (P = 0.0138) levels reduced PC risk, while phosphatidylcholine (16:0_20:3) (P = 0.0295) and higher sphingomyelin (d40:1) (P = 0.0217) levels increased PC risk. Additionally, 22 immune cells had an effect on PC. Among those, only CD4 Regulatory T (Treg) AC cells played a mediating role between phosphatidylinositol (18:0_20:4) and PC (proportion mediated: 10.5%). No significant heterogeneity or pleiotropy was observed. The present study showed that PC risk was impacted by phosphatidylcholine, phosphatidylinositol, triacylglycerol, sterol ester, and sphingomyelin levels. The causal relationship between phosphatidylinositol (18:0_20:4) and PC was mediated by CD4 Treg AC cells, which provides insight for immunotherapy.https://doi.org/10.1038/s41598-025-05898-xMendelian randomization analysisPlasma lipidomePancreatic cancerImmune cell |
| spellingShingle | Chunhong Ma Dandan Liu Changchun Ye Zilu Chen Ranran Kong Jianzhong Li Xuejun Sun Zhengshui Xu Immune cells mediate the association between the plasma lipidome and pancreatic cancer: a Mendelian randomization analysis Scientific Reports Mendelian randomization analysis Plasma lipidome Pancreatic cancer Immune cell |
| title | Immune cells mediate the association between the plasma lipidome and pancreatic cancer: a Mendelian randomization analysis |
| title_full | Immune cells mediate the association between the plasma lipidome and pancreatic cancer: a Mendelian randomization analysis |
| title_fullStr | Immune cells mediate the association between the plasma lipidome and pancreatic cancer: a Mendelian randomization analysis |
| title_full_unstemmed | Immune cells mediate the association between the plasma lipidome and pancreatic cancer: a Mendelian randomization analysis |
| title_short | Immune cells mediate the association between the plasma lipidome and pancreatic cancer: a Mendelian randomization analysis |
| title_sort | immune cells mediate the association between the plasma lipidome and pancreatic cancer a mendelian randomization analysis |
| topic | Mendelian randomization analysis Plasma lipidome Pancreatic cancer Immune cell |
| url | https://doi.org/10.1038/s41598-025-05898-x |
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