单细胞测序技术在骨肉瘤中的研究进展
Research progress of single cell sequencing in osteosarcoma
严伟杰 1刘云 2罗恺 2杨明秀 2李善航 1贺聚良1
作者信息
- 1. 广西医科大学附属肿瘤医院骨软组织外科,南宁 530021
- 2. 广西医科大学第一附属医院脊柱骨病外科,南宁 530021
- 折叠
摘要
骨肉瘤是起源于骨组织的高度恶性肿瘤,具有病死率高、预后差的特点.肿瘤微环境的异质性是影响骨肉瘤发生发展及预后的关键.单细胞测序技术通过鉴定骨肉瘤组织中的肿瘤细胞、免疫细胞和基质细胞的功能特征和基因表达模式,描绘了细胞间复杂的交互网络,是解析肿瘤微环境异质性的重要手段.应用单细胞测序技术的高分辨率优势,在骨肉瘤组织中鉴定了 SPP1(+)巨噬细胞、C1QC(+)巨噬细胞和CLEC11A(+)B细胞等新的细胞亚型,它们在肿瘤微环境中起着促进肿瘤生长和侵袭的作用.通过对骨肉瘤干细胞亚群的鉴定,推测SERPINA1_CSCL1、FUS_CSCL2和SPP1_CSCL3这三群干细胞可能是骨肉瘤细胞的起源.运用单细胞测序发现mregDCs通过特异性表达CCR7、CCL17、CCL19和CCL22因子从而招募Treg细胞,促进免疫逃逸和肿瘤进展.此外,单细胞测序技术通过鉴定骨肉瘤耐药的潜在靶点,基于此建立耐药风险评分模型,为制定个性化的化疗方案提供依据.在疾病的预后方面,单细胞测序技术识别了骨肉瘤中与免疫浸润相关的基因(如EPHX2、FDPS、GBP1、MMD和ZYX),并以此构建了骨肉瘤的预后分析模型,对预测患者的预后具有指导意义.
Abstract
Osteosarcoma,a highly malignant tumor originating from bone tissue,is characterized by a high mortality along with a poor prognosis.The heterogeneity of the tumor microenvironment plays a pivotal role in its development and prognosis.Sin-gle-cell sequencing technology emerges as a crucial tool in elucidating this heterogeneity by delineating the functional characteris-tics and gene expression patterns of tumor cells,immune cells,and stromal cells within osteosarcoma tissues.This technology en-ables the depiction of the intricate interaction network between these cells.Utilizing the high-resolution advantage of single-cell se-quencing,novel cell subtypes such as SPP1(+)macrophages,C1QC(+)macrophages,and CLEC11A(+)B cells have been identi-fied in osteosarcoma tissues,contributing to tumor growth and invasion within the tumor microenvironment.Identification of osteo-sarcoma stem cell subpopulations suggests that SERPINA1_CSCLl,FUS_CSCL2,and SPP1_CSCL3 populations may serve as the origin of osteosarcoma cells.Moreover,single-cell sequencing has revealed that mregDCs promote immune escape and tumor pro-gression by selectively expressing CCR7,CCL17,CCL19,and CCL22 factors,thereby recruiting Treg cells.Additionally,this tech-nology aids in the development of personalized chemotherapy regimens by pinpointing potential drug resistance targets in osteosar-coma,leading to the establishment of a drug resistance risk score model.In terms of disease prognosis,single-cell sequencing has identified immune infiltration-associated genes in osteosarcoma(e.g.,EPHX2,FDPS,GBP1,MMD,ZYX),facilitating the construc-tion of a prognostic analysis model for osteosarcoma patients,thus aiding in prognostic prediction.
关键词
骨肉瘤/单细胞测序/肿瘤微环境/抗药性,肿瘤Key words
Osteosarcoma/Tumor microenvironment/Drug resistance,neoplasm/Single-cell sequencing引用本文复制引用
基金项目
南宁市青秀区科技基地和人才专项(2020068)
出版年
2024
NETL
NSTL
万方数据