Department of Orthopedics.
State Key Lab of Molecular Oncology and Immunology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Immunother. 2022;45(6):274-283. doi: 10.1097/CJI.0000000000000421. Epub 2022 May 10.
Guanylate binding protein 2 (GBP2) could bind to guanine nucleotides (GMP, GDP, and GTP) and exhibits antiviral activity against influenza virus through the innate immune response. Some researchers have demonstrated that the value of GBP2 in predicting the prognosis of multiple cancers and the complex correlation with immune response. However, the correlation of GBP2 to prognosis and immune cell infiltration level were unknown in skin cutaneous melanoma (SKCM). The GBP2 expression in multiple cancers were evaluated through Tumor Immune Estimation Resource (TIMER) and Oncomine. We also evaluated the influence of GBP2 on overall survival in multiple caners through GEPIA, TIMER, and tissue microarray. The correlation between GBP2 expression level and immune cell or gene markers of immune infiltration level was explored on TIMER and GEPIA. Gene set enrichment analysis was performed using the TCGA dataset. The GBP2 expression level represented a significant reduction and the GBP2 expression was lower compared with the SKCM-Metastasis with P<0.01. Lower GBP2 expression was significantly correlated with the poor overall survival of SKCM patients. Simultaneously, higher GBP2 expression predicted the better SKCM-free survival with P=0.019. GBP2 expression was positively correlated with the infiltration cells of B-cell, CD8+ T-cell, CD4+ T-cell, macrophage, neutrophil, and dendritic cell in SKCM. And there was a significant negative correlation between the expression of GBP2 and DNA methylation in the cBioPortal database (P=3.39e-42). Gene set enrichment analysis revealed that GBP2 was closely correlated with multiple pathways of immune response in cancer. In conclusion, Lower expression of GBP2 associated with less immune cell infiltration and poor prognosis in SKCM and the high promoter methylation of GBP2 represented a promising biomarker for poor prognostication in SKCM.
鸟苷酸结合蛋白 2（GBP2）可以与鸟嘌呤核苷酸（GMP、GDP 和 GTP）结合，并通过先天免疫反应发挥抗流感病毒的活性。一些研究人员已经证明，GBP2 在预测多种癌症的预后和与免疫反应的复杂相关性方面具有重要价值。然而，在皮肤黑色素瘤（SKCM）中，GBP2 与预后和免疫细胞浸润水平的相关性尚不清楚。通过 Tumor Immune Estimation Resource（TIMER）和 Oncomine 评估了 GBP2 在多种癌症中的表达。我们还通过 GEPIA、TIMER 和组织微阵列评估了 GBP2 对多种癌症总生存率的影响。通过 TIMER 和 GEPIA 探讨了 GBP2 表达水平与免疫细胞或免疫浸润水平基因标志物的相关性。使用 TCGA 数据集进行了基因集富集分析。结果显示，与 SKCM-Metastasis 相比，GBP2 的表达水平显著降低（P<0.01），并且表达水平较低。较低的 GBP2 表达与 SKCM 患者的总生存率显著相关。同时，较高的 GBP2 表达预示着 SKCM 无复发生存率更好（P=0.019）。GBP2 表达与 SKCM 中 B 细胞、CD8+T 细胞、CD4+T 细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润细胞呈正相关。并且在 cBioPortal 数据库中，GBP2 的表达与 DNA 甲基化呈显著负相关（P=3.39e-42）。基因集富集分析表明，GBP2 与癌症中多种免疫反应途径密切相关。总之，GBP2 表达水平降低与 SKCM 中免疫细胞浸润减少和预后不良相关，而 GBP2 启动子高甲基化可能是 SKCM 预后不良的有前途的生物标志物。
