The advent of liquid biopsy technologies has revolutionized our ability to monitor disease progression and treatment response non-invasively. Mass cytometry, with its high-dimensional capabilities, has emerged as a powerful tool in this field, offering unprecedented insights into circulating biomarkers. This chapter explores the application of mass cytometry to liquid biopsies, focusing on circulating tumor cells (CTCs), cell-free DNA, and extracellular vesicles.
Mass Cytometry Analysis of Circulating Tumor Cells
Circulating tumor cells provide a window into the molecular characteristics of tumors without the need for invasive tissue biopsies. Mass cytometry has significantly enhanced our ability to characterize these rare cells.
Gerdtsson et al. (2018) demonstrated the power of imaging mass cytometry (IMC) for multiplex protein detection on CTCs in their groundbreaking study published in Convergent Science Physical Oncology. They developed a method to simultaneously analyze 16 protein markers on individual CTCs, providing a comprehensive view of tumor cell heterogeneity in liquid biopsies. Intriguingly, this study used imaging mass cytometry to study liquid biopsies.
More recently, a study written by Payne et al. in Nature (2023) demonstrates the “feasibility of using mass cytometry to analyze circulating tumor cells (CTCs) from head and neck squamous cell carcinoma (HNSCC)” patients, enriched using the Parsortix microfluidic platform. CTCs were detected in 13 out of 14 HNSCC patients, with counts ranging from 2-24 CTCs/ml of blood. Using a 41-marker antibody panel, the researchers identified three main CTC subgroups: epithelial, early EMT, and advanced EMT, each with distinct phenotypic and signaling characteristics. Notably, the EMT status in CTCs did not correlate with the EMT profile of the primary tumor, suggesting independent adaptation of CTCs in circulation. Mass cytometry analysis outperformed bulk RNA sequencing in detecting CTCs and characterizing their phenotypes, revealing intra-patient heterogeneity that was not apparent in bulk analysis. This method provides a platform for high-dimensional proteomic characterization of CTCs at single-cell resolution, potentially enabling novel biomarker development and treatment stratification in HNSCC.
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