Cell State and Cell Type: Deconvoluting Circulating Tumor Cell Populations in Liquid Biopsies by Multi-Omics.

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Tumor-microenvironment interactions drive cancer progression, therapeutic resistance, and impact patient survival.
• Liquid biopsies offer a non-invasive method to study circulating tumor and microenvironment cells.

Purpose of the Study:

• To comprehensively analyze circulating rare cells (CRCs) from breast and prostate cancer patients.
• To delineate cancer cell lineages from other rare cells within the tumor microenvironment (TME).
• To associate circulating cells with disease status and progression.

Main Methods:

• Utilized a universal rare event detection platform (HDSCA) for Cytokeratin+, CD45- CRCs.
• Employed morphometrics, single-cell copy number analysis, and targeted multiplexed proteomics.
• Characterized epithelial circulating tumor cells (EPI.CTCs), epithelial-to-mesenchymal transition CTCs (EMT.CTCs), and circulating endothelial cells (CECs).

Main Results:

• Successfully detected EPI.CTCs, EMT.CTCs, and CECs.
• Longitudinal analysis showed CTCs at disease progression and CECs at stable disease.
• Observed significant inter-patient and temporal intra-patient variability in marker expression (ER, HER2, AR, PSA, PSMA, EpCAM).

Conclusions:

• Multi-omic characterization of CRCs is crucial for understanding breast and prostate carcinomas.
• Highlighted overlapping and cell-type-defining proteo-genomic features of CTCs and CECs.
• Emphasized the clinical relevance of analyzing circulating rare cells for disease monitoring.