ArticleJournal of experimental & clinical cancer research : CR2025
Phenotypic diversity of CTCs and tdEVs in liquid biopsies of tumour-draining veins is linked to poor prognosis in colorectal cancer.
Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Bridging the gap: a genetically validated avian chorioallantoic membrane platform for investigation of spontaneous circulating tumor cells.Molecular oncology · 2026Article
- A novel imaging-based approach for large extracellular vesicle detection and prognostic stratification in metastatic breast cancer.The journal of liquid biopsy · 2026Article
- Fast enrichment and detection of circulating tumor cells from large volumes of whole blood of breast cancer patients utilizing a functionalized bioaffinity CTC filtration membrane.International journal of cancer · 2026Article
- Clinical applications and future perspectives of circulating tumor cells in solid tumors.Discover oncology · 2026Review
- Review
- Biomimetic Membrane Interface Technologies for Detection and Isolation of CTCs and EVs: Advances and Opportunities in Liquid Biopsy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The ACCEPTance of automation: refining circulating tumor cells enumeration for improved metastatic colorectal cancer prognosis.Molecular oncology · 2025Article
- Liquid biopsy of circulating tumor cells: From isolation, enrichment, and genome sequencing to clinical applications.Histology and histopathology · 2025Review
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19 authors.
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Abstract
backgroundCirculating 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.
methodsCellSearch 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).
resultsCTCs and tdEVs were more abundant in the DV samples compared to CVC samples (p < 0.05). tdEVs were detected in higher numbers than CTCs in both compartments. Importantly, tdEVs in CVCs were associated with tumor spread, whereas CTCs in DVs were linked to tumor size. In both compartments, the prognostic value of tdEVs for overall survival (OS) surpassed that of CTCs, as demonstrated by univariate, multivariate, and Kaplan-Meier analyses. CTCs and tdEVs in DVs were phenotypically distinct, being larger, more eccentric, and displaying stronger cytokeratin intensities (p < 0.05) compared to those in CVC samples. Furthermore, increased diversity in CTC and tdEV phenotypes was significantly associated with shorter survival, validating the prognostic relevance of the SD-diversity metric.
conclusionOur study demonstrates that DV sampling significantly enhances the detection of prognostically relevant CTCs and tdEVs in CRC patients, underscoring the superior prognostic significance of tdEVs compared to CTCs. Importantly, the combined phenotypic diversity of both markers emerges as a more powerful biomarker than their enumeration alone. These findings suggest that comprehensive, automated analysis of CTCs and tdEVs in DVs may open new avenues for tailoring individualized therapies in CRC patients.
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