Dokument: Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis
| Titel: | Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=67264 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20241029-142900-7 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Stoecklein, Nikolas H. [Autor] Fluegen, Georg [Autor] Guglielmi, Rosa [Autor] Neves, Rui Lousa das [Autor] Hackert, Thilo [Autor] Birgin, Emrullah [Autor] Cieslik, Stefan A. [Autor] Sudarsanam, Monica [Autor] Driemel, Christiane [Autor] Dalum, Guus van [Autor] | |||||||
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| Stichwörter: | Liquid biopsy, DLA, CTC profiling, Pancreatic ductal adenocarcinoma, CTCs, Single cell genomics, High-blood volume analysis, Diagnostic leukapheresis, Circulating tumor cells, PDAC | |||||||
| Beschreibung: | The limited sensitivity of circulating tumor cell (CTC) detection in pancreatic adenocarcinoma (PDAC) stems from their extremely low concentration in the whole circulating blood, necessitating enhanced detection methodologies. This study sought to amplify assay-sensitivity by employing diagnostic leukapheresis (DLA) to screen large blood volumes. Sixty patients were subjected to DLA, with a median processed blood volume of ~ 2.8 L and approximately 5% of the resulting DLA-product analyzed using CellSearch (CS). Notably, DLA significantly increased CS-CTC detection to 44% in M0-patients and 74% in M1-patients, yielding a 60-fold increase in CS-CTC enumeration. DLA also provided sufficient CS-CTCs for genomic profiling, thereby delivering additional genomic information compared to tissue biopsy samples. DLA CS-CTCs exhibited a pronounced negative prognostic impact on overall survival (OS), evidenced by a reduction in OS from 28.6 to 8.5 months (univariate: p = 0.002; multivariable: p = 0.043). Additionally, a marked enhancement in sensitivity was achieved (by around 3-4-times) compared to peripheral blood (PB) samples, with positive predictive values for OS being preserved at around 90%. Prognostic relevance of CS-CTCs in PDAC was further validated in PB-samples from 228 PDAC patients, consolidating the established association between CTC-presence and reduced OS (8.5 vs. 19.0 months, p < 0.001). In conclusion, DLA-derived CS-CTCs may serve as a viable tool for identifying high-risk PDAC-patients and aiding the optimization of multimodal treatment strategies. Moreover, DLA enables comprehensive diagnostic profiling by providing ample CTC material, reinforcing its utility as a reliable liquid-biopsy approach. This high-volume liquid-biopsy strategy presents a potential pathway for enhancing clinical management in this malignancy. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Stoecklein, N. H., Flügen, G., Guglielmi, R., Lousa das Neves, R., Hackert, T., Birgin, E., Cieslik, S. A., Sudarsanam, M., Driemel, C., Dalum, G. van, Franken, A., Niederacher, D., Neubauer, H., Fehm, T., Rox, J. M., Böhme, P., Häberle, L., Göring, W., Esposito, I., … Rahbari, N. N. (2023). Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis. Molecular Cancer, 22(1), Article 181. https://doi.org/10.1186/s12943-023-01880-1 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 29.10.2024 | |||||||
| Dateien geändert am: | 29.10.2024 |
