陆军军医大学学报2026，Vol.48Issue(3)：272-282,11.DOI:10.16016/j.2097-0927.202512013
胃癌异质性转录元程序相关的微环境空间互作单元及临床意义分析
Spatial profiling of gastric cancer reveals distinct transcriptional meta-programs driving immunosuppressive microenvironment
摘要
Abstract
Objective To systematically characterize tumor microenvironmental features and spatial cellular interactomes associated with distinct transcriptional meta-program(MP)in gastric cancer,and explore their clinical implications.Methods We integrated 2 gastric cancer single-cell RNA sequencing(scRNA-seq)datasets to identify malignant cell-derived transcriptional MP.The prognostic value was validated in 3 independent bulk transcriptomic cohorts:The Cancer Genome Atlas(TCGA),GSE15459,and GSE66229.Using scRNA-seq,we dissected MP-specific shifts in microenvironmental cell composition and inferred dominant ligand-receptor interactions.Spatial transcriptomics confirmed the co-localization of implicated cell subsets and signaling pairs.Survival analyses were used to access the associations between key cellular signatures/interaction signatures and patient outcomes.Results Four MP from MP1 to MP4 were identified in malignant cells.High expression of MP2 and MP4 significantly correlated with worse overall survival(P<0.05).In MP2-high tumors,SPP1+macrophages were enriched and predicted to interact with T3 neutrophils via the SPP1-CD44 ligand-receptor pair,with spatial co-localization validated.Both SPP1+macrophage signature(P=0.007)and SPP1-CD44 interaction signature(P=0.008)predicted adverse prognosis.In MP4-high tumors,myofibroblastic cancer-associated fibroblast(myCAF)were expanded and showed interaction with exhausted CD8+T cells through the COL6A family-ITGB1 signaling axis,which was also spatially validated.The myCAF signature(P=0.001)and COL6A family-ITGB1 interaction signature(P<0.001)correlated with poorer survival.Conclusion MP2 and MP4 delineate 2 distinct immunosuppressive spatial niches in gastric cancer:SPP1+macrophage-T3 neutrophil and myCAF-exhausted CD8+T cell.These niches likely drive tumor progression via SPP1-CD44 and COL6A family-ITGB1 axes,respectively,providing potential targets for precision immunotherapy.关键词
胃癌/肿瘤异质性/单细胞转录组学/肿瘤微环境/空间转录组学Key words
gastric cancer/tumor heterogeneity/single-cell transcriptomics/tumor microenvironment/spatial transcriptomics分类
医药卫生引用本文复制引用
彭紫依,张永超,刘振昆,向俊宇,李先锋,邱秋,王斌..胃癌异质性转录元程序相关的微环境空间互作单元及临床意义分析[J].陆军军医大学学报,2026,48(3):272-282,11.基金项目
国家重点研发计划项目(2023YFC3402102,2022YFA1105302) （2023YFC3402102,2022YFA1105302）
重庆市研究生科研创新项目(CYS240815) Supported by the National Key Research and Development Program of China(2023YFC3402102,2022YFA1105302)and the Chongqing Graduate Research and Innovation Program(CYS240815). （CYS240815）
