Single-cell sequencing and its application in breast cancer.

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.