遗传 ›› 2020, Vol. 42 ›› Issue (3): 250-268.doi: 10.16288/j.yczz.19-268

• 综述 • 上一篇    下一篇

单细胞测序技术及其在乳腺癌研究中的应用

张强, 顾明亮()   

  1. 聊城市人民医院,转化医学研究联合实验室,聊城 252000
  • 收稿日期:2019-10-25 修回日期:2020-02-03 出版日期:2020-03-20 发布日期:2020-02-08
  • 通讯作者: 顾明亮 E-mail:minglianggu@hotmai.com
  • 作者简介:张强,硕士,实习研究员,研究方向:分子遗传学。E-mail: qiangzhang17@yeah.net
  • 基金资助:
    国家重点研发计划“干细胞及转化研究”重点专项编号(2018YFA0109500);山东省自然科学基金青年基金项目资助编号(ZR2019QH009)

Single-cell sequencing and its application in breast cancer

Qiang Zhang, Mingliang Gu()   

  1. Joint Laboratory for Translational Medicine Research, Liaocheng City People's Hospital, Liaocheng 252000, China
  • Received:2019-10-25 Revised:2020-02-03 Online:2020-03-20 Published:2020-02-08
  • Contact: Gu Mingliang E-mail:minglianggu@hotmai.com
  • Supported by:
    Supported by the National Key R&D Program of China No(2018YFA0109500);the Youth Fund of Natural Science Foundation of Shandong Province No(ZR2019QH009)

摘要:

乳腺癌是起源于乳腺各级导管和乳腺上皮细胞,由增生到不典型增生而逐步发展成原位癌、早期浸润癌至浸润性癌的一种恶性肿瘤。传统高通量测序技术对乳腺癌的研究主要是鉴定与乳腺癌发生发展相关的“驱动基因”,但是对于乳腺癌基因组结构变化以及亚克隆的鉴定等存在一定的局限性,并且忽略了乳腺癌肿瘤细胞之间的异质性。近年来兴起的单细胞测序技术是以单个细胞为研究对象,对基因拷贝和基因表达等数据进行分析,探究乳腺癌的细胞组成、细胞状态和细胞命运,绘制乳腺癌生态系统图谱,对临床患者进行精准分层,为实现个体化治疗提供支持。同时,还可以揭示乳腺癌与T细胞、巨噬细胞等免疫细胞间的相关性,为发现乳腺癌新的治疗靶点、免疫检查点等提供参考。本文对单细胞测序技术及其在乳腺癌研究中的应用和研究进展进行了综述,以期为单细胞测序技术的进一步发展提供参考,同时为理解乳腺癌的发病机制和免疫治疗提供基础支持。

关键词: 单细胞测序, 乳腺癌, 肿瘤微环境, 免疫治疗

Abstract:

Breast cancer originates from ducts and epithelial cells, and gradually develops from hyperplasia to atypical hyperplasia, in situ (adeno) carcinoma, to early and advanced invasive carcinoma. Traditional high-throughput sequencing mainly aims to identify candidate ‘driver genes’ attributable to development and progression of breast cancer, which has deficiencies in characterizing genomic structure alteration and subclone evolution, and thus ignores intratumoral, intertumoral or interpatient heterogeneity. The single-cell sequencing technology analyzes transcriptome (e.g., gene copy number and gene expression), explores cellular composition, differentiation and fate, fine-maps the tumor microenvironment, and provides supporting evidence for accurate stratification as well as personalized, precise therapy. At the same time, a complex relationship between breast cancer cells and T cells, macrophages and other immune cells can be revealed, thus facilitating discovery of new therapeutic targets and immune checkpoints. Here, we review state-of-the-art single-cell sequencing technologies and its application in breast cancer, in order to decipher multi-faceted alterations in the crosstalk/interactions between tumors and its microenvironments at the single-cell level, and provide a basis for better understanding of complicated pathogenesis and new avenues for immunotherapy.

Key words: single-cell sequencing, breast cancer, tumor microenvironment, immunotherapy