摘要:
目的 了解不同SDHx基因表达与嗜铬细胞瘤/副神经节瘤(pheochromocytoma/paraganglioma,PPGL)免疫细胞浸润的关系特点及差异。方法 从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中下载并整理PPGL的RNAseq数据,分别对SDHx家族的SDHA、SDHB、SDHC、SDHD和SDHAF2基因表达与24种免疫细胞浸润进行Spearman相关性分析,探讨SDHx家族中不同基因突变导致的PPGL肿瘤免疫细胞浸润差异。结果 相较于其他4个同族基因,SDHA特有的免疫细胞浸润特点为肿瘤微环境中具有与其表达呈正相关的树突状细胞(r=0.157,P=0.034)和未成熟的树突状细胞(r=0.150,P=0.043);SDHB特有的免疫细胞浸润特点为具有与其表达呈正相关的嗜酸性粒细胞(r=0.192,P=0.009)和Th17细胞(r=0.230,P=0.002),以及呈负相关的调节性T细胞(r=-0.160,P=0.030)和CD8+T细胞(r=-0.147,P=0.047);SDHC特有的免疫细胞浸润特点为具有与其表达呈正相关的效应记忆型T细胞(r=0.196,P=0.008)、Th2细胞(r=0.171,P=0.020)、T细胞(r=0.149,P=0.043)和中性粒细胞(r=0.149,P=0.043);SDHD特有的免疫细胞浸润特点为具有与其表达呈负相关的自然杀伤细胞(r=-0.173,P=0.019)和NK CD56bright细胞(r=-0.162,P=0.028);SDHAF2特有的免疫细胞浸润特点为具有与其表达呈正相关的浆细胞样树突状细胞(r=0.152,P=0.039),呈负相关的巨噬细胞(r=-0.187,P=0.011)和Th2细胞(r=-0.264,P<0.001)。在SDHB、SDHC和SDHD突变的PPGL中,均发现浆细胞样树突状细胞与基因表达成明显负相关关系(P均<0.05)。结论 SDHx基因家族的每个基因突变导致的PPGL免疫浸润细胞均有其自身特点,为针对不同特点的免疫浸润细胞探索相应的免疫治疗提供了可行研究方向。
Abstract:
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.
作者投稿
专家审稿
编辑办公
邮件订阅
RSS
下载:
