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Review
. 2023 Aug 2;24(15):12337.
doi: 10.3390/ijms241512337.

Deciphering the Biology of Circulating Tumor Cells through Single-Cell RNA Sequencing: Implications for Precision Medicine in Cancer

Affiliations
Review

Deciphering the Biology of Circulating Tumor Cells through Single-Cell RNA Sequencing: Implications for Precision Medicine in Cancer

Santhasiri Orrapin et al. Int J Mol Sci. .

Abstract

Circulating tumor cells (CTCs) hold unique biological characteristics that directly involve them in hematogenous dissemination. Studying CTCs systematically is technically challenging due to their extreme rarity and heterogeneity and the lack of specific markers to specify metastasis-initiating CTCs. With cutting-edge technology, single-cell RNA sequencing (scRNA-seq) provides insights into the biology of metastatic processes driven by CTCs. Transcriptomics analysis of single CTCs can decipher tumor heterogeneity and phenotypic plasticity for exploring promising novel therapeutic targets. The integrated approach provides a perspective on the mechanisms underlying tumor development and interrogates CTCs interactions with other blood cell types, particularly those of the immune system. This review aims to comprehensively describe the current study on CTC transcriptomic analysis through scRNA-seq technology. We emphasize the workflow for scRNA-seq analysis of CTCs, including enrichment, single cell isolation, and bioinformatic tools applied for this purpose. Furthermore, we elucidated the translational knowledge from the transcriptomic profile of individual CTCs and the biology of cancer metastasis for developing effective therapeutics through targeting key pathways in CTCs.

Keywords: circulating tumor cells; drug resistance; metastasis; personalized and precision medicine; single-cell RNA and transcriptome sequencing; tumor heterogeneity.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
An overview of CTC enrichment and single-cell RNA sequencing workflow.
Figure 2
Figure 2
A summary finding of the scRNA-seq analysis of CTCs and their potential targets for clinical relevance. (a) The representative promising drug targets for CTCs that were disclosed by scRNA-seq technology and the prospective for personalized medicine of individual CTCs by drug susceptibility tests. (b) The transcriptional and phenotypic heterogeneity of tumor cells in the transit journey of CTCs. As the intermediator conduit to metastasis, CTCs possess different phenotypic characteristics, including EMT and CSC phenotypes, drug resistance, CTCs coupled with immune cells, and extravasating CTCs. Thus, gene expression profiling of CTCs could accomplish a complete understanding of the significance of CTC dissemination and hold remarkable promise for advancing precision cancer therapy.

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