Causal relationship between palmitoylation genes mediated by immune cell phenotypes and oral cancer: A Mendelian randomized study

Palmitoylation plays a crucial role in the development of cancer, but the causal relationship with oral cancer is still uncertain. The aim of this study was to describe the causal relationship between palmitoylation modified genes and oral cancer, while identifying intermediate factors. Genome-wide association studies of immune cells, oral cancer, and palmitoylation gene expression quantitative trait locus were derived from public databases. In this study, inverse variance weighting was used as the primary analytical method to investigate the causal relationship between exposure and outcome. In addition, this study uses Mendelian randomization (MR) Egger, simple mode, weighted median and weighted mode as supplementary analysis methods. To ensure the reliability of the findings, we further assessed horizontal pleiotropy and heterogeneity, and used the leave-one-out method to assess the stability of the MR results. Finally, mediated analysis was used to elucidate the potential mediated role of immune cell phenotype. Two-sample MR analysis revealed a causal relationship between palmitoylation genes and oral cancer. The results showed that zinc finger DHHC-type containing 19 (odds ratio [OR] = 0.6482, 95% CI: 0.5335-0.7875, P < .001) was negatively correlated with the occurrence of oral cancer. Zinc finger DHHC-type (ZDHHC)2 (OR = 1.6051, 95% CI: 1.3389-1.9242, P < .001) and ZDHHC24 (OR = 1.6077, 95% CI: 1.1588-2.2305, P = .0045) were positively correlated with oral cancer. The results of mediated MR analysis showed that CD28+ CD45RA+ CD8br absolute cell counts positively regulated ZDHHC2 and oral cancer (mediation effect [ME] = 0.0801; mediation proportion [MP] = 16.92%). CD28- CD8br absolute cell counts (ME = 0.0747; MP = 17.23%) and CD25 on IgD- CD38dim (ME = 0.0164; MP = 3.78%) positively modulated ZDHHC19- oral cancer. This study provides evidence supporting a causal relationship between palmitoylation genes and oral cancer, with immune cell phenotypes acting as mediators. Identifying a potential causal relationship between palmitoylation genes and oral cancer reveals its underlying mechanisms and suggests new therapeutic targets.