南方医科大学学报2023，Vol.43Issue(5)：667-679,13.DOI:10.12122/j.issn.1673-4254.2023.05.01
FARSB对泛肿瘤的预后和冷肿瘤微环境的分层作用:基于整合单细胞和大块组织的DNA测序
FARSB stratifies prognosis and cold tumor microenvironment across different cancer types:an integrated single cell and bulk RNA sequencing analysis
摘要
Abstract
Objective Immunotherapy has brought significant clinical benefits to a subset of patients,but has thus far been disappointing in the treatment of immunologically"cold"tumors.Existing biomarkers that can precisely identify these populations are insufficient.In this context,a potential cold tumor microenvironment(TME)marker FARSBwas investigated to reveal its impact on TME and patients'response to immunotherapy across pan-cancer.Methods The expression levels and mutational landscape of FARSB in pan-cancer were investigated.Kaplan-Meier and univariate Cox regression analyses were applied to analyze the prognostic significance of FARSB.Pathways affected by FARSBwere investigated by gene set enrichment and variation analysis.The relationship between FARSBexpression and immune infiltration was examined using the TIMER2 and R packages.Single-cell RNA sequencing(scRNA-seq)data of several cancer types from GSE72056,GSE131907,GSE132465,GSE125449 and PMID32561858 were analyzed to validate the impact of FARSBon the TME.The predictive effect of FARSBon immunotherapy efficacy was explored in 3 immune checkpoint inhibitors(ICIs)-treated cohorts(PMID32472114,GSE176307,and Riaz2017).Results FARSB expression was significantly higher in 25 tumor tissues than in normal tissues and was associated with poor prognosis in almost all tumor types.FARSBexpression exhibited a strong association with several DNA damage repair pathways and was significantly associated with TP53 mutation in lung adenocarcinoma(P<0.0001,OR=2.25).FARSB characterized a typical immune desert TME and correlated with impaired expression of chemokines and chemokines receptors.Large-scale scRNA-seq analysis confirmed the immunosuppressive role of FARSBand revealed that FARSBpotentially shapes the cold TME by impeding intercellular interactions.In 3 ICI-treated cohorts,FARSB demonstrated predictive value for immunotherapy.Conclusion This study provides a pan-cancer landscape of the FARSB gene by integrated single-cell and bulk DNA sequencing analysis and elucidates its biological function to promote DNA damage repair and construct the immune desert TME,suggesting the potential value of FARSBas a novel marker for stratifying patients with poor immunotherapeutic benefits and"cold"TME.关键词
FARSB/免疫治疗/泛癌/DNA损伤修复/肿瘤微环境Key words
FARSB/immunotherapy/pan-cancer/DNA damage repair/tumor microenvironment引用本文复制引用
张自然,谭家乐,于子航,刘承栋,王剑,吴德华,白雪..FARSB对泛肿瘤的预后和冷肿瘤微环境的分层作用:基于整合单细胞和大块组织的DNA测序[J].南方医科大学学报,2023,43(5):667-679,13.基金项目
Supported by National Nature Science Foundation of China(82272731),Outstanding Youths Development Scheme of Nanfang Hospital(2020J011),Southern Medical University Nanfang Hospital President's Fund(B2020B023),and Guangdong Provincial Medical Research Fund(A2021064). 国家自然科学基金(82272731) （82272731）
南方医院杰出青年基金(2020J011) （2020J011）
南方医科大学南方医院院长基金(B2020B023) （B2020B023）
广东省医学科研基金(A2021064) （A2021064）
