Background <p>Circulating tumor cells (CTCs) and platelets might be collected simultaneously during liquid biopsy; however, their interaction in the form of platelet-covered CTCs (pcCTCs) remains only partially understood. In this study, we aimed to detect and characterize pcCTCs using single-cell data from peripheral blood mononuclear cells (PBMCs) and to compare their transcriptomic profiles with naked CTCs and platelets.</p> Methods <p>We analyzed 22 samples (10 from breast cancer patients and 12 from ovarian cancer patients) and 7 controls (3 non-malignant samples and 4 healthy donors) to identify candidate CTCs and pcCTCs.</p> Results <p>We identified 12 candidate CTCs: 5 naked CTCs and 7 pcCTCs in 5 patients in total. We next examined genes associated with epithelial–mesenchymal transition (EMT), angiogenesis, extracellular matrix organization, and platelet activation, signaling, and aggregation. These pathways were found to be upregulated in pcCTCs exhibiting the highest platelet-associated signal. We computed scores for epithelial and mesenchymal CTC phenotypes, platelet-related signatures, and gene sets associated with ovarian and breast cancer CTCs.</p> Conclusion <p>Transcriptomic analysis revealed that platelet cloaking significantly influences genes connected with CTCs survival in the bloodstream and metastatic progression.</p>

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Exploring platelet-covered and naked circulating tumor cells – a single-cell transcriptomic perspective

  • Michał Sieczczyński,
  • Krzysztof Pastuszak,
  • Marcin Banacki,
  • Kamil Łangowski,
  • Sylwia Łapińska-Szumczyk,
  • Anna Samelak-Czajka,
  • Paulina Jackowiak,
  • Iwona Inkielewicz-Stepniak,
  • Anna Supernat,
  • Anna Joanna Żaczek

摘要

Background

Circulating tumor cells (CTCs) and platelets might be collected simultaneously during liquid biopsy; however, their interaction in the form of platelet-covered CTCs (pcCTCs) remains only partially understood. In this study, we aimed to detect and characterize pcCTCs using single-cell data from peripheral blood mononuclear cells (PBMCs) and to compare their transcriptomic profiles with naked CTCs and platelets.

Methods

We analyzed 22 samples (10 from breast cancer patients and 12 from ovarian cancer patients) and 7 controls (3 non-malignant samples and 4 healthy donors) to identify candidate CTCs and pcCTCs.

Results

We identified 12 candidate CTCs: 5 naked CTCs and 7 pcCTCs in 5 patients in total. We next examined genes associated with epithelial–mesenchymal transition (EMT), angiogenesis, extracellular matrix organization, and platelet activation, signaling, and aggregation. These pathways were found to be upregulated in pcCTCs exhibiting the highest platelet-associated signal. We computed scores for epithelial and mesenchymal CTC phenotypes, platelet-related signatures, and gene sets associated with ovarian and breast cancer CTCs.

Conclusion

Transcriptomic analysis revealed that platelet cloaking significantly influences genes connected with CTCs survival in the bloodstream and metastatic progression.