Applications of single-cell sequencing in cancer research: progress and perspectives

Abstract

Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics sequencing, is a powerful tool to decipher the cellular and molecular landscape at a single-cell resolution, unlike bulk sequencing, which provides averaged data. The use of single-cell sequencing in cancer research has revolutionized our understanding of the biological characteristics and dynamics within cancer lesions. In this review, we summarize emerging single-cell sequencing technologies and recent cancer research progress obtained by single-cell sequencing, including information related to the landscapes of malignant cells and immune cells, tumor heterogeneity, circulating tumor cells and the underlying mechanisms of tumor biological behaviors. Overall, the prospects of single-cell sequencing in facilitating diagnosis, targeted therapy and prognostic prediction among a spectrum of tumors are bright. In the near future, advances in single-cell sequencing will undoubtedly improve our understanding of the biological characteristics of tumors and highlight potential precise therapeutic targets for patients.

Keywords: Circulating tumor cells; Heterogeneity; Microenvironment; Single-cell sequencing.

Fig. 1

Application of single-cell sequencing in delineating tumor heterogeneity and designing novel targeted therapies for patients with various tumors. a Single-cell sequencing can be used to analyze differentially expressed genes (DEGs), thereby detecting key genes and signaling pathways that are altered during tumor progression and constructing a regulatory network and clonality trees within tumor lesions. When DEGs are combined with canonical markers, the cells are clustered, which enables the identification of rare subpopulations, cell states and phenotype switches during tumor progression. Interrogation of the tumor microenvironment (TME) and heterogeneity enables the disclosure of therapeutic resistance mechanisms and the design of novel therapies. b Single-cell sequencing explores tumor heterogeneity at distinct levels, including the population, individual cell, tissue and molecular levels

Fig. 2

Schematic of tumor metastasis and interactions between circulating tumor cells (CTCs) and peripheral cells. a Tumor metastasis is a complex process that includes invasion of the primary tumor border, intravasation, survival in the circulatory system, extravasation and the formation of a micrometastatic niche in distant tissues. b However, CTCs in the circulatory system dynamically interact with peripheral cells, and CNCs are very important. E: estrogen; CTCs: circulating tumor cells; CNCs: circulating tumor cell and neutrophil niches