datasheet3_Role of PRDM1 in Tumor Immunity and Drug Response: A Pan-Cancer Analysis.csv

Background: PR domain zinc finger protein 1 (PRDM1) is a regulator of both B cell and T cell differentiation and plays a critical role in immunosuppression. Its role in tumor immunity and correlation with drug response remain unknown.Methods: This work comprehensively analyzed the transcriptional expression pattern of the PRDM1 among 33 types of malignancies from The Cancer Genome Atlas and the Genotype-Tissue Expression projects. Besides, correlation of the PRDM1 with cancer prognosis, immune infiltrates, checkpoint markers, cancer stemness and drug response were explored.Results: High expression level of PRDM1 were observed in ACC, COAD, LAML, LGG, LUAD, OV, PAAD, STAD, TGCT. Cox regression model showed high expression of PRDM1 in tumor samples correlates with poor prognosis in LGG, PAAD, UVM while favorable prognosis in KIRC, SKCM and THCA. PRDM1 expression positively correlates with the expression of LAG3, CTLA4, PDCD1 (PD-1), CD274 (PD-L1), PDCD1LG2 (PD-L2), TIGIT in the majority of 33 cancer types. PRDM1 positively correlated with TNFRSF14 in LGG and UVM among cancers with unfavorable prognosis; this correlation were weak or even negative in cancers with favorable prognosis. The top negatively enriched KEGG terms in high PRDM1 subgroup were B cell receptor signaling, T cell receptor signaling, and the top negatively enriched HALLMARK terms included IL-2-STAT5 signaling and allograft rejection. The expression of PRDM1 was found positively correlated with cancer stemness in CHOL, KIRP, TGCT, THYM and UVM. A series of targeted drugs and small-molecule drugs with promising efficacy predicted by PRDM1 level were identified.Conclusion: The clinical significance and biological impact of high transcriptional expression of PRDM1 differs across different cancers. Inhibiting the PRDM1-dependent signaling could be a novel and promising strategy of immunotherapy in cancers including LGG, PAAD and UVM.

背景：PR域锌指蛋白1（PRDM1）是B细胞和T细胞分化的调节因子，在免疫抑制中发挥着至关重要的作用。其在肿瘤免疫中的作用以及与药物反应的相关性尚不清楚。方法：本研究全面分析了来自癌症基因组图谱和基因型-组织表达项目的33种恶性肿瘤中PRDM1的转录表达模式。此外，还探讨了PRDM1与癌症预后、免疫浸润、检查点标记、肿瘤干细胞和药物反应的相关性。结果：在ACC、COAD、LAML、LGG、LUAD、OV、PAAD、STAD、TGCT等肿瘤中观察到PRDM1的高表达水平。Cox回归模型显示，肿瘤样本中PRDM1的高表达与LGG、PAAD、UVM中的不良预后相关，而在KIRC、SKCM和THCA中则与良好预后相关。在33种癌症类型的大多数中，PRDM1的表达与LAG3、CTLA4、PDCD1（PD-1）、CD274（PD-L1）、PDCD1LG2（PD-L2）、TIGIT的表达呈正相关。在不良预后的癌症中，PRDM1与LGG和UVM中的TNFRSF14呈正相关；而在良好预后的癌症中，这种相关性较弱或甚至为负。在高PRDM1亚组中，最负相关的KEGG术语包括B细胞受体信号传导、T细胞受体信号传导，最负相关的HALLMARK术语包括IL-2-STAT5信号传导和同种异体移植物排斥。在CHOL、KIRP、TGCT、THYM和UVM中，PRDM1的表达与肿瘤干细胞呈正相关。通过PRDM1水平预测，一系列靶向药物和小分子药物显示出有前景的疗效。结论：PRDM1转录高表达的临床意义和生物学影响在不同癌症中存在差异。抑制PRDM1依赖的信号传导可能成为包括LGG、PAAD和UVM在内的癌症免疫治疗的一种新颖且具有前景的策略。