Causal relationships between immune cells, inflammatory factors, serum metabolites, and hepatic cancer: A two-sample...

Observational studies and clinical trials suggest associations between immune cells, inflammatory factors, serum metabolites, and hepatic cancer. However, the causal relationships between these factors and hepatic cancer remain to be established.

To explore the causal relationships between immune cells, inflammatory factors, serum metabolites, and hepatic cancer.

This study employed comprehensive two-sample Mendelian randomization (MR) utilizing publicly available genetic data (GWAS) to analyze causal relationships between 731 immune cell traits, 91 inflammatory factors, 1400 serum metabolites, and hepatic cancer. The primary analysis used inverse variance-weighted (IVW) MR, with additional sensitivity tests to assess the validity of causal relationships.

After correction for heterogeneity and horizontal pleiotropy, in exploring the causal relationships between immune cell groups and hepatic cancer, we found that Terminally Differentiated CD4^-CD8^- T cell %T cell was negatively associated with hepatic cancer, serving as a protective factor, while Effector Memory CD4^-CD8^- T cell %CD4^-CD8^- T cell was positively associated with hepatic cancer, acting as a risk factor. In investigating the causal relationships between inflammatory factors and hepatic cancer, C-C motif chemokine 19 levels were positively associated with hepatic cancer, representing a risk factor, while Interleukin-10 levels were negatively associated with hepatic cancer, acting as a protective factor. Regarding the causal relationships between serum metabolites and hepatic cancer, (N(1) + N(8))-acetylspermidine levels were negatively associated with hepatic cancer, serving as a protective factor, while 1-(1-enyl-palmitoyl)-GPC (p-16:0) levels were positively associated with hepatic cancer, acting as a risk factor.

Our MR analysis indicates causal relationships between immune cells, inflammatory factors, serum metabolites, and hepatic cancer. However, further validation is needed to assess the potential of these immune cells, inflammatory factors, and serum metabolites as preventive or therapeutic targets for hepatic cancer.