中国癌症防治杂志2025，Vol.17Issue(6)：705-714,10.DOI:10.3969/j.issn.1674-5671.2025.06.08
多组学分析揭示Y染色体丢失在膀胱癌中的作用及临床意义
Multi-omics analysis reveals the role and clinical significance of the loss of Y chromosome in bladder cancer
摘要
Abstract
Objective To investigate the role and clinical significance of the loss of Y chromosome(LOY)in bladder cancer.Methods Tissue samples and clinical data were collected from 44 male patients with bladder cancer undergoing radical cystectomy at the First Affiliated Hospital of Guangxi Medical University between January 2018 and October 2019.Whole-transcriptome sequencing data were analyzed and scored based on Y chromosome transcriptional signature(YchrS)using single-sample gene set enrichment analysis(ssGSEA).Patients were stratified into high and low YchrS score groups.The prognosis of the two groups were evaluated using the Kaplan-Meier method,and the potential molecular characteristics were revealed via differential expression analysis and gene set enrichment analysis(GSEA).The diversity of immune cells in the two groups was analyzed using cytometry by time of flight(CyTOF).Single-cell transcriptomic sequencing data from a public database(HRA000212)was used to characterize LOY epithelial cells through cell differen-tiation trajectories and cell communication analysis.The CMap database was utilized to identify potential therapeutic agents.Results Patients with bladder cancer in the low YchrS score group exhibited shorter overall survival(P=0.006)and higher tumor grade(P=0.036).Upregulated genes in low YchrS score group were enriched in biological processes related to the cell cycle regulation,DNA replication,and chromosome segregation(P<0.05),showing elevated scores for p53-repressed genes and reduced scores for p53-induced genes(all P<0.001).Compared with other epithelial cells,LOY epithelial cells displayed activation of immune-related signaling pathways and stronger interactions with myeloid cells and T cells.CyTOF analysis revealed an enrichment of regulatory T(Treg)cells and upregulated expression of CD279(PD-1)on CD4+T cells in the low YchrS score group.CMap analysis indicated that cyclin-dependent kinase(CDK)inhibitors(e.g.,Palbociclib)and histone deacetylase(HDAC)inhibitors were potential therapeutic agents for bladder cancer patients in the low YchrS score group.Conclusions LOY is strongly associated with poor prognosis in bladder cancer patients,with its tumorigenic mechanism may involve p53 suppression and immune suppression.CDK inhibitors and HDAC inhibitors serve as potential therapeutic agents for the LOY bladder cancer patients.关键词
膀胱癌/Y染色体丢失/肿瘤微环境/调节性T细胞Key words
Bladder cancer/Loss of Y chromosome/Tumor microenvironment/Regulatory T cells分类
医药卫生引用本文复制引用
刘涛,覃泽足,冯超,郑又文,汤绍梅,王秋雁,李天宇..多组学分析揭示Y染色体丢失在膀胱癌中的作用及临床意义[J].中国癌症防治杂志,2025,17(6):705-714,10.基金项目
国家自然科学基金项目(82560483) （82560483）
广西自然科学基金项目(2025GXNSFAA069715) （2025GXNSFAA069715）
广西重点研发计划项目(桂科AB25069011) （桂科AB25069011）
广西研究生教育创新计划项目(YCSW2025288) （YCSW2025288）
