单细胞测序技术在肝癌研究中的应用

Application of Single Cell Sequencing Technology in Hepatocellular Carcinoma Research

传统的细胞遗传信息研究方法是对大量混合细胞进行高通量测序,得到一群细胞基因表达的平均值,忽视了细胞间存在的异质性。肝癌作为一种人类常见的恶性致命肿瘤,其内部肿瘤细胞存在高度异质性,群体水平分析无法精确揭示其恶性细胞克隆结构和免疫微环境的细胞种类、状态和亚群分布,因此迫切需要进行单细胞水平的分析,这将有助于深入了解肝癌发病机制,进行精准肝癌分型指导临床治疗。同时发现,新型治疗靶点及有效生物标记物,为肝癌患者今后进行精准诊疗提供参考。本文综述了单细胞基因组和转录物组测序技术在肝癌免疫微环境、肝癌细胞异质性、肝癌细胞演化与诊疗和肝癌转移机制及生物标志物研究中的应用。本文还总结了在肝癌研究中,单细胞多组学测序技术在发现新肿瘤亚群、精确识别肿瘤细胞间的异质性和了解肿瘤微环境构成等方面的优势。

Traditional bulk tumor analysis with high-throughput DNA sequencing yields an average of gene expression in a population of cells,ignoring the heterogeneity between tumor cells.Hepatocellular carcinoma is one of the most common malignant tumors of human beings,with an obvious intratumor heterogeneity.The analysis of cell population could not accurately determine the clonal structures of tumor cells and identity the cell types,status and subpopulation distribution of immune microenvironment.The analysis at single-cell resolution is necessary to reveal the subpopulation of multiple malignant cells within tumors,as well as the cell types and their status in tumor microenvironment,promoting to find new therapeutic targets and effective biomarkers in clinical diagnosis,subtyping and treatment.This paper reviews the application of single-cell DNA and RNA sequencing technology in the study of hepatocellular carcinoma immune microenvironment,heterogeneity,clonal evolution,metastasis mechanism and biomarkers discovery.In addition,we also summarize the advantages of single cell multiomic sequencing in finding new tumor subsets,accurately identifying the heterogeneity of tumor cells and understanding the composition of tumor microenvironment.