Induction of circulating ABCB1 transcripts under platinum-based chemotherapy indicates poor prognosis and a bone micrometastatic phenotype in ovarian cancer patients.

Autor: Schwarz FM; Department of Gynaecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; National Center for Tumour Diseases (NCT), Dresden, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.; German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany., Kuhlmann JD; Department of Gynaecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; National Center for Tumour Diseases (NCT), Dresden, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.; German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany., Kämpfer J; Department of Gynaecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; National Center for Tumour Diseases (NCT), Dresden, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.; German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany., Klimova A; National Center for Tumour Diseases (NCT), Dresden, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.; Institute for Medical Informatics and Biometry, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany., Klotz DM; Department of Gynaecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; National Center for Tumour Diseases (NCT), Dresden, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.; German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany., Freitag L; Department of Gynaecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; National Center for Tumour Diseases (NCT), Dresden, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.; German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany., Herrmann P; Experimental and Clinical Research Center, Department of Translational Oncology of Solid Tumours, Charité - Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, Berlin, D-13125, Germany., Zinnow V; Experimental and Clinical Research Center, Department of Translational Oncology of Solid Tumours, Charité - Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, Berlin, D-13125, Germany., Smith J; Experimental and Clinical Research Center, Department of Translational Oncology of Solid Tumours, Charité - Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, Berlin, D-13125, Germany., Scheller T; Experimental Pharmacology & Oncology GmbH, Berlin-Buch, Germany., Walther W; Experimental and Clinical Research Center, Department of Translational Oncology of Solid Tumours, Charité - Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, Berlin, D-13125, Germany., Wimberger P; Department of Gynaecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; National Center for Tumour Diseases (NCT), Dresden, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.; German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany., Stein U; Experimental and Clinical Research Center, Department of Translational Oncology of Solid Tumours, Charité - Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, Berlin, D-13125, Germany. ustein@mdc-berlin.de.; German Cancer Consortium (DKTK), Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany. ustein@mdc-berlin.de.
Jazyk: angličtina
Zdroj: Molecular cancer [Mol Cancer] 2024 Aug 23; Vol. 23 (1), pp. 174. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1186/s12943-024-02087-8
Abstrakt: The drug efflux transporter P-glycoprotein, encoded by the ABCB1 gene, promotes acquired chemoresistance. We explored the presence and clinical relevance of circulating cell-free ABCB1 transcripts (cfABCB1 tx ) in ovarian cancer patients (173 longitudinal serum samples from 79 cancer patients) using digital droplet PCR. cfABCB1 tx  were readily detectable at primary diagnosis (median 354 mRNA copies/20 µl serum), paralleled FIGO-stage and predicted surgical outcome (p = 0.023, p=0.022, respectively). Increased cfABCB1 tx levels at primary diagnosis indicated poor PFS (HR = 2.329, 95%CI:1.374-3.947, p = 0.0017) and OS (HR = 2.074, 95%CI:1.194-3.601, p = 0.0096). cfABCB1 tx induction under platinum-based chemotherapy was an independent predictor for poor OS (HR = 2.597, 95%CI: 1.218-5.538, p = 0.013) and paralelled a micrometastatic phenotype, shaped by the presence of disseminated tumor cells in the bone marrow. A strong correlation was observed between cfABCB1 tx and circulating transcripts of the metastasis-inducer MACC1, which is the transcriptional activator of ABCB1. Combined assessment of cfABCB1 tx and circulating cell-free MACC1 transcripts (cfMACC1 tx ) resulted in an improved prognostic prediction, with  the cfABCB1 tx -high/cfMACC1 tx -high phenotype bearing the highest risk for relapse and death. Conclusively, we provide proof of principle, that ABCB1 transcripts are readily traceable in the liquid-biopsy of ovarian cancer patients, advancing a new dimension for systemic monitoring of ABCB1/P-glycoprotein expression dynamics.
(© 2024. The Author(s).)
Databáze: MEDLINE
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