基于单细胞测序数据的骨肉瘤预后相关细胞亚群特征分析  

Characterization of Cell Subsets Associated With Prognosis of Osteosarcoma Based on Single-Cell Sequencing Data

作　　者：王胜涛 朱浩然 徐淑娟 贵鹏 陈明洲 李朝旭 WANG Shengtao;ZHU Haoran;XU Shujuan;GUI Peng;CHEN Mingzhou;LI Zhaoxu(Department of Joint Surgery and Sports Medicine,Nanxishan Hospital of Guangxi Zhuang Autonomous Region,Guilin,Guangxi 541002,China;Zonglian College,Xi’an Jiaotong University,Xi’an 710061,China;Department of Hematology,Affiliated Hospital of Guilin Medical University,Guilin,Guangxi 541001,China;Department of Trauma and Hand Surgery,Nanxishan Hospital of Guangxi Zhuang Autonomous Region,Guilin,Guangxi 541002,China)

机构地区：[1]广西壮族自治区南溪山医院关节外科与运动医学科,广西桂林541002 [2]西安交通大学宗濂书院,西安710061 [3]桂林医学院附属医院血液内科,广西桂林541001 [4]广西壮族自治区南溪山医院创伤骨科与手外科,广西桂林541002

出　　处：《中国医学科学院学报》2023年第5期773-782,共10页Acta Academiae Medicinae Sinicae

基　　金：广西医疗卫生重点培育学科建设项目(桂卫教科发[2022]4号)。

摘　　要：目的 通过分析不同骨肉瘤患者肿瘤组织的细胞组成,探究与骨肉瘤预后相关的细胞亚群及特征。方法 下载不同患者骨肉瘤单细胞测序数据及bulk测序数据,提取细胞样本信息进行降维、注释、细胞功能分析,明确与骨肉瘤预后相关的细胞种类,鉴定骨肉瘤预后相关细胞特征。分析具有预后意义的巨噬细胞发育轨迹,根据分化空间差异基因构建骨肉瘤预后模型。结果 不同骨肉瘤患者的细胞组成存在异质性。骨肉瘤中浸润的单核巨噬细胞具有显著预后意义(P=0.003)。4类巨噬细胞组成关键预后单核巨噬细胞亚群,其特征性转录调控因子包括RUNX3(+)、ETS1(+)、HOXD11(+)、ZNF281(+)、PRRX1(+)。巨噬细胞亚群的预后能力随骨肉瘤的恶性进展而增强,其中Prog_Macro2及Prog_Macro4亚群巨噬细胞位于发育轨迹终端。基于巨噬细胞分化差异基因的预后模型能够有效区分不同风险骨肉瘤患者的生存率(P<0.001)。结论 巨噬细胞亚群与骨肉瘤预后密切相关,可作为骨肉瘤免疫治疗的关键靶细胞。Objective To explore the cell subsets and characteristics related to the prognosis of osteosarcoma by analyzing the cellular composition of tumor tissue samples from different osteosarcoma patients.Methods The single-cell sequencing data and bulk sequencing data of different osteosarcoma patients were downloaded.We extracted the information of cell samples for dimensionality reduction,annotation,and cell function analysis,so as to identify the cell subsets and clarify the cell characteristics related to the prognosis of osteosarcoma.The development trajectory of macrophages with prognostic significance was analyzed,and the prognostic model of osteosarcoma was established based on the differentially expressed genes of macrophage differentiation.Results The cellular composition presented heterogeneity in the patients with osteosarcoma.The infiltration of mononuclear phagocytes in osteosarcoma had prognostic significance(P=0.003).Four macrophage subsets were associated with prognosis,and their signature transcription factors included RUNX3(+),ETS1(+),HOXD11(+),ZNF281(+),and PRRX1(+).Prog_Macro2 and Prog_Macro4 were located at the end of the developmental trajectory,and the prognostic ability of macrophage subsets increased with the progression of osteosarcoma.The prognostic model established based on the differentially expressed genes involved in macrophage differentiation can distinguish the survival rate of osteosarcoma patients with different risks(P<0.001).Conclusion Macrophage subsets are closely related to the prognosis of osteosarcoma and can be used as the key target cells for the immunotherapy of osteosarcoma.

关 键 词：骨肉瘤 单细胞测序 单核巨噬细胞系统 巨噬细胞 预后 

分 类 号：R738.1[医药卫生—肿瘤]