摘要
目的 构建膀胱癌雄激素受体(androgen receptors,AR)相关基因评分系统,并探究不同AR评分膀胱癌患者肿瘤微环境特征。方法 基于TCGA-BLCA队列,根据文献报道中的AR相关基因集,构建评分系统,并在GSE-13507队列及自有的29例膀胱癌临床样本中进行验证;应用转录组学和高通量的单细胞质谱流式技术揭示高AR评分组及低AR评分组膀胱癌患者的分子特征及肿瘤微环境异质性。结果 基于TCGA-BLCA队列构建了膀胱癌AR相关基因评分系统。TCGA-BLCA队列和GSE-13507队列分析结果显示,高AR评分组膀胱癌患者的总生存期(overall survival,OS)明显比低AR评分组差(P=0.009,0.010);临床样本分析结果虽然无明显统计学意义但同样显示高AR评分组患者的OS较低AR评分组患者差(P=0.180),且高AR评分组患者的临床分期更晚,病理分级更高。高AR评分组与低AR评分组患者具有不同的分子特征,且肿瘤微环境存在异质性,其中免疫抑制性CD4+T细胞亚群13以及具有免疫抑制表型特征的肿瘤干样细胞亚群13在高AR评分组富集。结论 本研究构建了一个AR相关基因的评分系统,其中高AR评分组患者的预后较低AR评分组患者差,且高AR评分组患者的肿瘤微环境免疫抑制状态更严重,其免疫治疗响应可能更高,更适合进行免疫治疗。
Objective To construct a scoring system for androgen receptors (AR)-related genes in bladder cancer and to explore the characteristics of the tumour microenvironment in bladder cancer patients with different AR scores.MethodsBased on the TCGA-BLCA cohort,the scoring system was constructed based on the set of AR-related genes reported in the literature,and validated in the GSE-13507 cohort and 29 self-owned clinical samples of bladder cancer.Transcriptomics and high-throughput single-cell mass spectrometry flow-acquisition techniques were applied to reveal molecular features and tumour microenvironmental heterogeneity of bladder cancer patients in the high and low AR score groups.ResultsAn AR-related gene scoring system for bladder cancer was constructed based on the TCGA-BLCA cohort.The results of the TCGA-BLCA cohort and GSE-13507 cohort analyses showed that the overall survival (OS) of bladder cancer patients in the high AR score group was significantly worse than that in the low AR score group (P=0.009,0.010).Although the results of the clinical sample analyses were not statistically significant,the OS of patients in the high AR score group was worse than that in the low AR score group (P=0.180),and patients in the high AR score group had later clinical stage and higher pathological grading.The patients in the low and high AR score groups had different molecular profiles,with heterogeneous tumour microenvironments,and enriched in the high AR score group were immunosuppressive CD4~+T-cell subpopulation 13 and characteristic tumour stem-like cell subpopulation 13 with an immunosuppressive phenotype.ConclusionsA scoring system for AR-related genes was constructed in this study,in which patients in the high AR scoring group had a poorer prognosis than that in the low AR score group,and patients in the high AR score group had more severe immunosuppressive state of the tumour microenvironment,probably showing higher re-sponse to immunotherapy,and becoming more suitable for immunotherapy.
作者
莫晗
刘桧
冯超
谢远亮
王秋雁
李天宇
MO Han;LIU Hui;FENG Chao;XIE Yuanliang;WANG Qiuyan;LI Tianyu(Department of Urology,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Center for Genomic and Personalized Medicine,Guangxi Medical University,Nanning 530021,China;Department of Urology,Guangxi Medical University Cancer Hosptial,Nanning 530021,China)
出处
《中国癌症防治杂志》
CAS
2023年第5期556-563,共8页
CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT
基金
国家自然科学基金项目(82060460
82160501)。
关键词
膀胱癌
雄激素受体
肿瘤微环境
质谱流式技术
Bladder Cancer
Tumor microenvironment
Androgen receptor
Mass cytometry
