Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China.
Cancer Commun (Lond). 2020 Aug;40(8):329-344. doi: 10.1002/cac2.12078. Epub 2020 Jul 12.
Single-cell RNA sequencing (scRNA-seq) is a novel technology that allows transcriptomic analyses of individual cells. During the past decade, scRNA-seq sensitivity, accuracy, and efficiency have improved due to innovations including more sensitive, automated, and cost-effective single-cell isolation methods with higher throughput as well as ongoing technological development of scRNA-seq protocols. Among the variety of current approaches with distinct features, researchers can choose the most suitable method to carry out their research. By profiling single cells in a complex population mix, scRNA-seq presents great advantages over traditional sequencing methods in dissecting heterogeneity in cell populations hidden in bulk analysis and exploring rare cell types associated with tumorigenesis and metastasis. scRNA-seq studies in recent years in the field of breast cancer research have clustered breast cancer cell populations with different molecular subtypes to identify distinct populations that may correlate with poor prognosis and drug resistance. The technology has also been used to explain tumor microenvironment heterogeneity by identifying distinct immune cell subsets that may be associated with immunosurveillance and are potential immunotherapy targets. Moreover, scRNA-seq has diverse applications in breast cancer research besides exploring heterogeneity, including the analysis of cell-cell communications, regulatory single-cell states, immune cell distributions, and more. scRNA-seq is also a promising tool that can facilitate individualized therapy due to its ability to define cell subsets with potential treatment targets. Although scRNA-seq studies of therapeutic selection in breast cancer are currently limited, the application of this technology in this field is prospective. Joint efforts and original ideas are needed to better implement scRNA-seq technologies in breast cancer research to pave the way for individualized treatment management. This review provides a brief introduction on the currently available scRNA-seq approaches along with their corresponding strengths and weaknesses and may act as a reference for the selection of suitable methods for research. We also discuss the current applications of scRNA-seq in breast cancer research for tumor heterogeneity analysis, individualized therapy, and the other research directions mentioned above by reviewing corresponding published studies. Finally, we discuss the limitations of current scRNA-seq technologies and technical problems that remain to be overcome.
单细胞 RNA 测序 (scRNA-seq) 是一种新兴技术，可对单个细胞进行转录组分析。在过去的十年中，由于包括更灵敏、自动化和更具成本效益的单细胞分离方法在内的创新，单细胞 RNA 测序的灵敏度、准确性和效率得到了提高，这些方法具有更高的通量，并且 scRNA-seq 技术协议也在不断发展。在具有不同特征的各种当前方法中，研究人员可以选择最合适的方法来进行研究。通过对复杂群体混合物中的单个细胞进行分析，scRNA-seq 在解析批量分析中隐藏的细胞群体异质性以及探索与肿瘤发生和转移相关的罕见细胞类型方面，比传统测序方法具有更大的优势。近年来，在乳腺癌研究领域的 scRNA-seq 研究已经将乳腺癌细胞群体聚类为不同的分子亚型，以鉴定可能与预后不良和耐药性相关的不同群体。该技术还通过鉴定可能与免疫监视相关且可能成为潜在免疫治疗靶点的独特免疫细胞亚群，用于解释肿瘤微环境异质性。此外，scRNA-seq 在乳腺癌研究中的应用除了探索异质性之外还有很多，包括细胞间通讯、调节性单细胞状态、免疫细胞分布等分析。scRNA-seq 也是一种很有前途的工具，由于其能够定义具有潜在治疗靶点的细胞亚群，因此可以促进个体化治疗。尽管目前乳腺癌中治疗选择的 scRNA-seq 研究有限，但该技术在该领域的应用前景广阔。需要共同努力和创新思路，以便更好地将 scRNA-seq 技术应用于乳腺癌研究，为个体化治疗管理铺平道路。本文简要介绍了目前可用的 scRNA-seq 方法及其优缺点，可为研究中合适方法的选择提供参考。我们还通过综述相应的已发表研究，讨论了 scRNA-seq 在乳腺癌肿瘤异质性分析、个体化治疗及上述其他研究方向的当前应用，并讨论了当前 scRNA-seq 技术的局限性和仍需克服的技术问题。
