Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Sichuan Province, Guoxue Xiang #37, Chengdu, 610041, China.
Eur J Med Res. 2023 Feb 2;28(1):55. doi: 10.1186/s40001-023-01012-x.
N7-methylguanosine (m7G) is closely associated with tumor prognosis and immune response in many cancer types. The correlation between m7G and bladder cancer (BC) needs further study. We aimed to orchestrate molecular subtypes and identify key genes for BC from the perspective of m7G.
RNA-seq and clinical data of BC patients were extracted from TCGA and GSE13507 datasets. The patients were subtyped by "ConsensusClusterPlus" and "limma." The clusters were validated by the Kaplan‒Meier curves, univariable and multivariate Cox regression models, the concordance index, and calibration curves. The immunotherapy response was evaluated by immune checkpoints, immune infiltration, TIDE score, and IMvigor210 cohort. Genomics of Drug Sensitivity in Cancer was utilized to predict the chemotherapy response between the clusters.
The m7G-related cluster was ultimately established by EIF4G1, NUDT11, NUDT10, and CCNB1. The independent prognostic value of the m7G-related cluster was validated by the TCGA and GSE13507 datasets. The cluster was involved in immune-associated pathways, such as neutrophil degranulation, antigen processing cross-presentation, and signaling by interleukins pathways. Meanwhile, cluster 2 was positively correlated with many immune checkpoints, such as CD274, CTLA4, HAVCR2, LAG3, PDCD1, and PDCD1LG2. The cluster 2 was significantly correlated with a higher TIDE score than the cluster 1. Furthermore, in the IMvigor210 cohort, patients in the cluster 1 had a higher response rate than those in the cluster 2. Patients in the cluster 2 were sensitive to many chemotherapies.
We successfully determined molecular subtypes and identified key genes for BC from the perspective of m7G, thereby providing a roadmap for the evolution of immunotherapy and precision medicine.
N7-甲基鸟嘌呤（m7G）与许多癌症类型的肿瘤预后和免疫反应密切相关。m7G 与膀胱癌（BC）之间的相关性需要进一步研究。我们旨在从 m7G 的角度构建分子亚型并确定 BC 的关键基因。
从 TCGA 和 GSE13507 数据集提取 BC 患者的 RNA-seq 和临床数据。使用“ConsensusClusterPlus”和“limma”对患者进行亚型分类。通过 Kaplan-Meier 曲线、单变量和多变量 Cox 回归模型、一致性指数和校准曲线验证聚类。通过免疫检查点、免疫浸润、TIDE 评分和 IMvigor210 队列评估免疫治疗反应。癌症药物敏感性基因组学用于预测聚类之间的化疗反应。
最终通过 EIF4G1、NUDT11、NUDT10 和 CCNB1 建立了 m7G 相关聚类。TCGA 和 GSE13507 数据集验证了 m7G 相关聚类的独立预后价值。该聚类与中性粒细胞脱颗粒、抗原加工交叉呈递和白细胞介素途径信号等免疫相关途径有关。同时，聚类 2 与许多免疫检查点呈正相关，如 CD274、CTLA4、HAVCR2、LAG3、PDCD1 和 PDCD1LG2。聚类 2 与较高的 TIDE 评分显著相关，而聚类 1 则较低。此外，在 IMvigor210 队列中，聚类 1 中的患者比聚类 2 中的患者有更高的缓解率。聚类 2 中的患者对许多化疗药物敏感。
我们成功地从 m7G 的角度确定了 BC 的分子亚型和关键基因，为免疫治疗和精准医学的发展提供了蓝图。
