Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2025
Genetic evidence for the causal impact of immune cells on pancreatic neuroendocrine tumors and the mediating effects of cathepsins.
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Tan Jiehui, Hao Yijie, Zhou Caihong, Tan Jinmei, Chen Wenhao, Liu Jiawei, Li Yanjie, Xu Jianliang, Lin Nan
Аннотация
OBJECTIVES: Pancreatic neuroendocrine tumors (pNETs) are a rare yet increasingly prevalent subset of pancreatic neoplasms with distinct biological characteristics. This study aimed to explore the causal relationships among immune cell traits, cathepsins, and pNETs.
METHODS: We conducted a two-sample Mendelian randomization (MR) analysis utilizing genome-wide association study (GWAS) data to investigate the causal effects of 731 immune cell traits and nine cathepsins on pNETs risk. The inverse-variance weighted (IVW) method was primarily used, supplemented by additional MR techniques. Bayesian Weighted Mendelian Randomization (BWMR) and other sensitivity analyses were employed to validate the findings and assess potential biases.
RESULTS: Our MR analysis identified significant causal associations between multiple immune cell traits and pNETs, including an increased risk associated with Plasmacytoid Dendritic Cell (%Dendritic Cell) and CD4-CD8- Natural Killer T cell (%lymphocyte). Conversely, other traits like Naive-mature B cell Absolute Count were associated with a decreased risk. Elevated levels of cathepsin E were also linked to an increased risk of pNETs, while cathepsin H was associated with a reduced risk. No reverse causality or significant pleiotropy was detected. Cathepsin E mediated the causal effects of CD4-CD8- Natural Killer T cell (%lymphocyte) on pNETs.
CONCLUSIONS: This study provides novel insights into the causal roles of immune cell traits and cathepsins in pNETs progression. The findings highlight potential targets for therapeutic intervention, emphasizing the complex interplay between the immune system and tumor biology in pNETs.
METHODS: We conducted a two-sample Mendelian randomization (MR) analysis utilizing genome-wide association study (GWAS) data to investigate the causal effects of 731 immune cell traits and nine cathepsins on pNETs risk. The inverse-variance weighted (IVW) method was primarily used, supplemented by additional MR techniques. Bayesian Weighted Mendelian Randomization (BWMR) and other sensitivity analyses were employed to validate the findings and assess potential biases.
RESULTS: Our MR analysis identified significant causal associations between multiple immune cell traits and pNETs, including an increased risk associated with Plasmacytoid Dendritic Cell (%Dendritic Cell) and CD4-CD8- Natural Killer T cell (%lymphocyte). Conversely, other traits like Naive-mature B cell Absolute Count were associated with a decreased risk. Elevated levels of cathepsin E were also linked to an increased risk of pNETs, while cathepsin H was associated with a reduced risk. No reverse causality or significant pleiotropy was detected. Cathepsin E mediated the causal effects of CD4-CD8- Natural Killer T cell (%lymphocyte) on pNETs.
CONCLUSIONS: This study provides novel insights into the causal roles of immune cell traits and cathepsins in pNETs progression. The findings highlight potential targets for therapeutic intervention, emphasizing the complex interplay between the immune system and tumor biology in pNETs.