Genetic Determinants of Immune Cells and Hepatocellular Carcinoma Risk: A Bioinformatics and Bidirectional Mendelian Randomization Study

Objective: This study aims to identify core targets in hepatocellular carcinoma (HCC) using bioinformatics and specific algorithms, to explore their relationships with immune cells, and to investigate the causal relationships between immune cells and HCC through Mendelian randomization.
Methods: Relevant genes associated with the development of HCC were screened using the GEO and TCGA databases. Immune infiltration analysis was conducted using GSVA and CIBERSORT algorithms. A bidirectional Mendelian randomization analysis was then performed to explore the causal relationships between immune cells and HCC.
Results: A total of 284 HCC-related genes were identified, with 120 genes recognized within the protein interaction network. Immune infiltration analysis revealed significant correlations between key genes and immune cells. Mendelian randomization results indicated that HLA DR on CD33+ HLA DR+ CD14dim (OR=1.0971, 95%CI:1.0019–1.2013, P=0.0453, P_Bonferroni=0.0906) and CD8 on CD28+ CD45RA+ CD8+ T cell (OR=1.1227, 95%CI: 1.0267–1.2276, P=0.0112, P_Bonferroni=0.0224) are risk factors for HCC. Conversely, HLA DR++ monocyte Absolute Count was identified as a protective factor for HCC (OR=0.8119, 95%CI: 0.7024–0.9383, P=0.0048, P_Bonferroni=0.1385).
Conclusion: This study, integrating bioinformatics with Mendelian randomization, comprehensively reveals the genetic mechanisms of HCC development and its relationship with immune cells from a genetic perspective for the first time. These findings provide guidance for future personalized treatment strategies for HCC.