Relationship Between Expressions of SDHx Genes and Immune Cell Infiltration in Pheochromocytoma/Paraganglioma

Objective To investigate the characteristics and differences of immune cell infiltration between different SDHx gene expression and pheochromocytoma/paraganglioma (PPGL). Methods RNAseq data of PPGL were downloaded and organized from The Cancer Genome Atlas (TCGA) database. Spearman correlation analysis was performed to assess the relationship between the expression of SDHx family genes (SDHA, SDHB, SDHC, SDHD, and SDHAF2) and the infiltration of 24 types of immune cells. Analyze the infiltrating immune cells in PPGL tumors caused by mutations in each gene in the SDHx family and the differences in immune cell infiltration of different genes. Results Compared to the other four syngeneic genes, SDHA exhibited unique immune cell infiltration characteristics, with dendritic cells (r=0.157, P=0.034) and immature dendritic cells (r=0.150, P=0.043) showing positive correlations with its expression in the tumor microenvironment. SDHB displayed unique immune cell infiltration features, including positive correlations with eosinophils (r=0.192, P=0.009) and Th17 cells (r=0.230, P=0.002), and negative correlations with regulatory T cells (r=-0.160, P=0.030) and CD8⁺ T cells (r=-0.147, P=0.047). SDHC showed unique immune cell infiltration characteristics, with positive correlations with effector memory T cells (r=0.196, P=0.008), Th2 cells (r=0.171, P=0.020), T cells (r=0.149, P=0.043), and neutrophils (r=0.149, P=0.043). SDHD exhibited unique immune cell infiltration features, with negative correlations with natural killer cells (r=-0.173, P=0.019) and NK CD56bright cells (r=-0.162, P=0.028). SDHAF2 demonstrated unique immune cell infiltration characteristics, with positive correlations with plasmacytoid dendritic cells (r=0.152, P=0.039) and negative correlations with macrophages (r=-0.187, P=0.011) and Th2 cells (r=-0.264, P<0.001). In PPGL with SDHB, SDHC, and SDHD mutations, plasmacytoid dendritic cells were significantly negatively correlated with gene expression (all P<0.05). Conclusion Each gene mutation in the SDHx gene family leads to distinct immune cell infiltration characteristics in PPGL, providing a feasible research direction for exploring targeted immunotherapies based on the unique immune cell infiltration patterns.