■免疫细胞在胰腺癌的发生发展中起着至关重要的作用,然而,由于复杂的免疫微环境和相互矛盾的研究结果,因果关系仍然不确定。孟德尔随机化(MR),本研究旨在阐明免疫细胞与胰腺癌之间的因果关系,同时确定中介因素。
■关于免疫细胞的全基因组关联研究(GWAS)数据,胰腺癌,和血浆代谢物来自公共数据库。在这次调查中,方差逆加权(IVW)是调查暴露与结果之间因果关系的主要分析方法。此外,这项研究纳入了MR-Egger,简单模式,加权中位数,和加权模式作为补充分析方法。为了确保我们发现的可靠性,我们进一步评估了水平多效性和异质性,并使用Leave-one方法评估了MR结果的稳定性.总之,本研究采用中介分析来阐明血浆代谢物的潜在中介效应.
■我们的研究揭示了免疫细胞与胰腺癌之间的因果关系,强调CD11c+单核细胞的关键作用(比值比,ORIVW=1.105;95%置信区间,95CI:1.002-1.218;P=0.045),HLA-DR+CD4+抗原呈递细胞(ORIVW=0.920;95CI:0.873-0.968;P=0.001),和HLA-DR+CD8brT细胞(ORIVW=1.058;95CI:1.002-1.117;P=0.041)在胰腺癌进展中的作用。进一步的调解分析表明,草酸盐(调解效应占总效应的比例:-11.6%,95%CI:-89.7%,66.6%)和甘露糖与反式4-羟脯氨酸的比率(-19.4,95%CI:-136%,96.8%)部分介导HLA-DR+CD8brT细胞与胰腺癌性质的关系。此外,我们的分析表明,肾上腺(-8.39%,95%CI:-18.3%,1.54%)在CD11c+单核细胞与胰腺癌的关联中起部分介导作用,而可的松(-26.6%,95%CI:138%,-84.8%)是HLADRCD4AC和胰腺癌之间的部分介质。
■这项MR调查提供了支持免疫细胞与胰腺癌之间因果关系的证据,血浆代谢物作为介质。鉴定对胰腺癌具有潜在因果效应的免疫细胞表型揭示了其潜在机制,并提出了新的治疗靶标。
UNASSIGNED: Immune cells play a crucial role in the development and progression of pancreatic cancer, yet the causal relationship remains uncertain due to complex immune microenvironments and conflicting research findings. Mendelian randomization (MR), this study aims to delineate the causal relationships between immune cells and pancreatic cancer while identifying intermediary factors.
UNASSIGNED: The genome-wide association study (GWAS) data on immune cells, pancreatic cancer, and plasma metabolites are derived from public databases. In this investigation, inverse variance weighting (IVW) as the primary analytical approach to investigate the causal relationship between exposure and outcome. Furthermore, this study incorporates MR-Egger, simple mode, weighted median, and weighted mode as supplementary analytical approaches. To ensure the reliability of our findings, we further assessed horizontal pleiotropy and heterogeneity and evaluated the stability of MR results using the Leave-one-out method. In conclusion, this study employed mediation analysis to elucidate the potential mediating effects of plasma metabolites.
UNASSIGNED: Our investigation revealed a causal relationship between immune cells and pancreatic cancer, highlighting the pivotal roles of CD11c+ monocytes (odds ratio, ORIVW=1.105; 95% confidence interval, 95%CI: 1.002-1.218; P=0.045), HLA DR+ CD4+ antigen-presenting cells (ORIVW=0.920; 95%CI: 0.873-0.968; P=0.001), and HLA DR+ CD8br T cells (ORIVW=1.058; 95%CI: 1.002-1.117; P=0.041) in pancreatic cancer progression. Further mediation analysis indicated that oxalate (proportion of mediation effect in total effect: -11.6%, 95% CI: -89.7%, 66.6%) and the mannose to trans-4-hydroxyproline ratio (-19.4, 95% CI: -136%, 96.8%) partially mediate the relationship between HLA DR+ CD8br T cells and pancreatic cancer in nature. In addition, our analysis indicates that adrenate (-8.39%, 95% CI: -18.3%, 1.54%) plays a partial mediating role in the association between CD11c+ monocyte and pancreatic cancer, while cortisone (-26.6%, 95% CI: 138%, -84.8%) acts as a partial mediator between HLA DR+ CD4+ AC and pancreatic cancer.
UNASSIGNED: This MR investigation provides evidence supporting the causal relationship between immune cell and pancreatic cancer, with plasma metabolites serving as mediators. Identifying immune cell phenotypes with potential causal effects on pancreatic cancer sheds light on its underlying mechanisms and suggests novel therapeutic targets.