Spatial transcriptomics of gastric cancer brain metastasis reveals atypical vasculature strategies with supportive immune profiles  

作　　者：Kaijing Liu Ying Wang Chunhua Wang Chengcheng Guo Dun Zhang Yu Zhong Lin Yin Yunxin Lu Furong Liu Yang Zhang Dongsheng Zhang 

机构地区：[1]Department of Medical Oncology,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong,P.R.China [2]State Key Laboratory of Oncology in South China,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China [3]Department of Radiation Oncology,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong,P.R.China [4]Department of Pathology,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong,P.R.China [5]Department of Neurosurgery/Neuro-oncology,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong,P.R.China [6]AccuraMed Technology(Guangzhou)Co.,Ltd,Guangzhou,Guangdong,P.R.China [7]Department of Clinical Research,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong,P.R.China [8]Integrated Traditional Chinese and Western Medicine Research Center,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong,P.R.China

出　　处：《Gastroenterology Report》2024年第1期336-347,共12页胃肠病学报道(英文)

基　　金：supported by the National Natural Science Foundation of China[82172711];the Natural Science Foundation of Guangdong Province[2019A1515011786];the Bethune Charitable Foundation[zllcaxw-15].

摘　　要：Background:Gastric cancer brain metastasis(GCBM)represents a rare but highly aggressive malignancy.Metastatic cancer cells are highly heterogeneous and differentially remodels brain vasculature and immune microenvironments,which affects the treatment effectiveness and patient outcome.This study aimed to investigate the spatial interactions among different cell components,espe-cially the vasculature system and the brain microenvironment of GCBM patients.Methods:We used digital spatial profiling to examine 140 regions composing tumor,immune,and brain tissues from three GCBM patients.Transcriptomic data with spatial information were analyzed for tissue areas related to different blood recruitment strategies.For validation,independent analysis of patient bulk transcriptomic data and in vivo single-cell transcriptomic data were performed.Results:Angiogenesis and blood vessel co-option co-existed within the same GCBM lesion.Tumors with high epithelial-mesenchymal transition and an enhanced transcriptomic gene signature composed of CTNNB1,SPARC,VIM,SMAD3,SMAD4,TGFB1,TGFB2,and TGFB3 were more prone to adopt blood vessel co-option than angiogenesis.Enriched macrophage infiltration,angiogenic chemokines,and NAMPT were found in angiogenic areas,while increased T cells,T cell activating cytokines,and reduced NAMPT were found in vessel co-option regions.Spatially,angiogenesis was enriched at the tumor edge,which showed higher DMBT1 expres-sion than the tumor center.Conclusions:This study mapped the orchestrated spatial characteristics of tumor and immunological compositions that support the conventional and atypical vascularization strategies in GCBM.Our data provided molecular insights for more effective combinations of anti-vascular and immune therapies.

关 键 词：gastric cancer brain metastases spatial transcriptomics angiogenesis blood vessel co-option tumor microenvironment 

分 类 号：R73-37[医药卫生—肿瘤]