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Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis

Authors :
Nikolas H. Stoecklein
Georg Fluegen
Rosa Guglielmi
Rui P.L. Neves
Thilo Hackert
Emrullah Birgin
Stefan A. Cieslik
Monica Sudarsanam
Christiane Driemel
Guus van Dalum
André Franken
Dieter Niederacher
Hans Neubauer
Tanja Fehm
Jutta M. Rox
Petra Böhme
Lena Häberle
Wolfgang Göring
Irene Esposito
Stefan A. Topp
Frank A.W. Coumans
Jürgen Weitz
Wolfram T. Knoefel
Johannes C. Fischer
Ulrich Bork
Nuh N. Rahbari
Source :
Molecular Cancer, Vol 22, Iss 1, Pp 1-7 (2023)
Publication Year :
2023
Publisher :
BMC, 2023.

Abstract

Abstract 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

Details

Language :
English
ISSN :
14764598
Volume :
22
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Molecular Cancer
Publication Type :
Academic Journal
Accession number :
edsdoj.5c1826cd9d794cc9bba8643ba9c0536e
Document Type :
article
Full Text :
https://doi.org/10.1186/s12943-023-01880-1