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

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 le...

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Main Authors: Stoecklein, Nikolas Hendrik (Author) , Flügen, Georg Erhard Wilhelm (Author) , Guglielmi, Rosa (Author) , Lousa das Neves, Rui (Author) , Hackert, Thilo (Author) , Birgin, Emrullah (Author) , Cieslik, Stefan Alexander (Author) , Sudarsanam, Monica (Author) , Driemel, Christiane (Author) , Dalum, Guus van (Author) , Franken, André (Author) , Niederacher, Dieter (Author) , Neubauer, Hans (Author) , Fehm, Tanja (Author) , Rox, Jutta Maria (Author) , Böhme, Petra (Author) , Häberle, Lena (Author) , Göring, Wolfgang (Author) , Esposito, Irene (Author) , Topp, Stefan (Author) , Coumans, Frank A.W. (Author) , Weitz, Jürgen (Author) , Knoefel, Wolfram T. (Author) , Fischer, Johannes (Author) , Bork, Ulrich (Author) , Rahbari, Nuh Nabi (Author)
Format: Article (Journal)
Language:English
Published: 13 November 2023
In: Molecular cancer
Year: 2023, Volume: 22, Issue: 1, Pages: 1-7
ISSN:1476-4598
DOI:10.1186/s12943-023-01880-1
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1186/s12943-023-01880-1
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Author Notes: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 and Nuh N. Rahbari
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Summary: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.
Item Description:Gesehen am 18.03.2024
Physical Description:Online Resource
ISSN:1476-4598
DOI:10.1186/s12943-023-01880-1

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