Unveiling the intricate causal nexus between pancreatic cancer and peripheral metabolites through a comprehensive bidirectional two-sample Mendelian randomization analysis

Frontiers in Molecular Biosciences

Molecular Biosciences

Haoyu Xu¹  Bin Zhou¹  Rong Sun¹  Feng Liu¹  Xiangdong Sun²  Minli Li³ 

[1] Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China;null;[e-mail];

关键词: pancreatic cancer;    peripheral metabolites;    two-sample Mendelian randomization;    high-density lipoprotein;    very low-density lipoprotein;   

DOI  :  10.3389/fmolb.2023.1279157

 received in 2023-08-17, accepted in 2023-10-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

Aim: Pancreatic cancer (PC) is a devastating malignancy characterized by its aggressive nature and poor prognosis. However, the relationship of PC with peripheral metabolites remains not fully investigated. The study aimed to explore the causal linkage between PC and peripheral metabolite profiles.Methods: Employing publicly accessible genome-wide association studies (GWAS) data, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis. The primary analysis employed the inverse-variance weighted (IVW) method. To address potential concerns about horizontal pleiotropy, we also employed supplementary methods such as maximum likelihood, weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO).Results: We ascertained 20 genetically determined peripheral metabolites with causal linkages to PC while high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) particles accounted for the vast majority. Specifically, HDL particles exhibited an elevated PC risk while VLDL particles displayed an opposing pattern. The converse MR analysis underscored a notable alteration in 17 peripheral metabolites due to PC, including branch chain amino acids and derivatives of glycerophospholipid. Cross-referencing the bidirectional MR results revealed a reciprocal causation of PC and X-02269 which might form a self-perpetuating loop in PC development. Additionally, 1-arachidonoylglycerophosphocholine indicated a reduced PC risk and an increase under PC influence, possibly serving as a negative feedback regulator.Conclusion: Our findings suggest a complex interplay between pancreatic cancer and peripheral metabolites, with potential implications for understanding the etiology of pancreatic cancer and identifying novel early diagnosis and therapeutic targets. Moreover, X-02269 may hold a pivotal role in PC onset and progression.

【 授权许可】

Unknown   
Copyright © 2023 Sun, Xu, Liu, Zhou, Li and Sun.