Abstract:  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. Methods Based 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. Results An 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. Conclusions A 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 response to immunotherapy, and becoming more suitable for immunotherapy.

Key words:  Bladder Cancer, Tumor microenvironment, Androgen receptor, Mass cytometry