Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis
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 diag...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12943-023-01880-1 |
| _version_ | 1797577670990495744 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nikolas H. Stoecklein |
| collection | DOAJ |
| description | 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 < 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. |
| first_indexed | 2024-03-10T22:12:18Z |
| format | Article |
| id | doaj.art-5c1826cd9d794cc9bba8643ba9c0536e |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-03-10T22:12:18Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-5c1826cd9d794cc9bba8643ba9c0536e2023-11-19T12:34:12ZengBMCMolecular Cancer1476-45982023-11-012211710.1186/s12943-023-01880-1Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysisNikolas H. Stoecklein0Georg Fluegen1Rosa Guglielmi2Rui P.L. Neves3Thilo Hackert4Emrullah Birgin5Stefan A. Cieslik6Monica Sudarsanam7Christiane Driemel8Guus van Dalum9André Franken10Dieter Niederacher11Hans Neubauer12Tanja Fehm13Jutta M. Rox14Petra Böhme15Lena Häberle16Wolfgang Göring17Irene Esposito18Stefan A. Topp19Frank A.W. Coumans20Jürgen Weitz21Wolfram T. Knoefel22Johannes C. Fischer23Ulrich Bork24Nuh N. Rahbari25General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfGeneral, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfGeneral, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfGeneral, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfDepartment of General, Visceral, and Transplantation Surgery, Heidelberg University HospitalDepartment of Surgery, Medical Faculty Mannheim, University Hospital MannheimGeneral, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfGeneral, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfGeneral, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfGeneral, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfDepartment of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfDepartment of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfDepartment of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfDepartment of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfDepartment of Transplantation Diagnostics and Cell Therapeutics, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfInstitute of Forensic Medicine Düsseldorf, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfInstitute of Pathology, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfInstitute of Pathology, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfInstitute of Pathology, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfGeneral, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfDecisive ScienceGeneral, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfGeneral, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfDepartment of Transplantation Diagnostics and Cell Therapeutics, University Hospital and Medical Faculty of the Heinrich-Heine-University DüsseldorfDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus of the Technical University DresdenDepartment of Surgery, Medical Faculty Mannheim, University Hospital MannheimAbstract 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.https://doi.org/10.1186/s12943-023-01880-1Pancreatic ductal adenocarcinomaPDACCirculating tumor cellsCTCsHigh-blood volume analysisLiquid biopsy |
| spellingShingle | 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 Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis Molecular Cancer Pancreatic ductal adenocarcinoma PDAC Circulating tumor cells CTCs High-blood volume analysis Liquid biopsy |
| title | Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis |
| title_full | Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis |
| title_fullStr | Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis |
| title_full_unstemmed | Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis |
| title_short | Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis |
| title_sort | ultra sensitive ctc based liquid biopsy for pancreatic cancer enabled by large blood volume analysis |
| topic | Pancreatic ductal adenocarcinoma PDAC Circulating tumor cells CTCs High-blood volume analysis Liquid biopsy |
| url | https://doi.org/10.1186/s12943-023-01880-1 |
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