Phenotypic diversity of CTCs and tdEVs in liquid biopsies of tumour-draining veins is linked to poor prognosis in colorectal cancer

• Published in: Journal of experimental & clinical cancer research 2025-01, Vol.44 (1), p.9-11, Article 9
• Main Authors: Cieslik, Stefan A, Zafra, Andrés G, Driemel, Christiane, Sudarsanam, Monica, Cieslik, Jan-Philipp, Flügen, Georg, Dizdar, Levent, Krieg, Andreas, Vaghiri, Sascha, Ashmawy, Hany, Fung, Stephen, Wilms, Miriam, Terstappen, Leon W M M, Nanou, Afroditi, Neubauer, Hans, Rahbari, Nuh N, Knoefel, Wolfram T, Stoecklein, Nikolas H, Neves, Rui P L
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Blood; Cells; Circulating tumour cells; Colorectal cancer; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Colorectal Neoplasms - surgery; CRC; CTCs; Development and progression; Extracellular Vesicles - metabolism; Extracellular Vesicles - pathology; Female; Health aspects; Humans; Liquid Biopsy - methods; Male; Medical examination; Metastasis; Middle Aged; Neoplastic Cells, Circulating - pathology; Phenotype; Prognosis; tdEVs; Tumour-derived extracellular vesicles
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-024-03259-6

Circulating tumour cells (CTCs) and tumour-derived extracellular vesicles (tdEVs) have great potential for monitoring therapy response and early detection of tumour relapse, facilitating personalized adjuvant therapeutic strategies. However, their low abundance in peripheral blood limits their informative value. In this study, we explored the presence of CTCs and tdEVs collected intraoperatively from a tumour-draining vein (DV) and via a central venous catheter (CVC) prior to tumour resection. CellSearch analyses of 395 blood samples from 306 patients with gastrointestinal tumours and 93 blood samples from healthy donors were used to establish and validate gates for the automated detection of CTCs and tdEVs with ACCEPT software and R scripts. The selected gate settings were applied to 227 samples of 142 patients with colorectal cancer (CRC) from two independent collectives. Phenotypic features were obtained via numeric analysis of their fluorescence signals (e.g. size, shape, and intensity) and were used for calculating diversity using Shannon index (SI) of clusters generated via the k-means algorithm after Uniform Manifold Approximation and Projection (UMAP) pre-processing, and standard deviation (SD). CTCs and tdEVs were more abundant in the DV samples compared to CVC samples (p