Journal
CLINICAL CHEMISTRY
Volume 62, Issue 11, Pages 1504-1515Publisher
AMER ASSOC CLINICAL CHEMISTRY
DOI: 10.1373/clinchem.2016.260299
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Funding
- Grant Agency of the Czech Republic [P303-16-10214S]
- ERDF [BIOCEV CZ.1.05/1.1.00/02.0109]
- MEYS
- MEYS [BIOCEV-FAR LQ1604 NPU II]
- City of Hamburg, Landesexzellenzinitiative Hamburg
- ERC
- TRANSCAN ERA-Network
- Innovative Medicines Initiative Joint Undertaking [115749]
- European Union
- EFPIA
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BACKGROUND: Transcriptome analysis of circulating tumor cells (CTCs) holds great promise to unravel the biology of cancer cell dissemination and identify expressed genes and signaling pathways relevant to therapeutic interventions. METHODS: CTCs were enriched based on their EpCAM expression (CellSearch (R)) or by size and deformability (Parsortix (TM)), identified by EpCAM and/or pan keratin-specific antibodies, and isolated for single cell multiplex RNA profiling. RESULTS: Distinct breast and prostate CTC expression signatures could be discriminated from RNA profiles of leukocytes. Some CTCs positive for epithelial transcripts (EpCAM and KRT19) also coexpressed leukocyte/mesenchymal associated markers (PTPRC and VIM). Additional subsets of CTCs within individual patients were characterized by divergent expression of genes involved in epithelial-mesenchymal transition (e.g., CDH2, MMPs, VIM, or ZEB1 and 2), DNA repair (RAD51), resistance to cancer therapy (e.g., AR, AR-V7, ERBB2, EGFR), cancer sternness (e.g., CD24 and CD44), activated signaling pathways involved in tumor progression (e.g., PIK3CA and MTOR) or cross talks between tumors and immune cells (e.g., CCL4, CXCL2, CXCL9, IL15, IL1B, or IL8). CONCLUSIONS: Multimarker RNA profiling of single CTCs reveals distinct CTC subsets and provides important insights into gene regulatory networks relevant for cancer progression and therapy. (C) 2016 American Association for Clinical Chemistry
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