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Article

Non-Invasive Profiling of Advanced Prostate Cancer via Multi-Parametric Liquid Biopsy and Radiomic Analysis

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Division of Medical Oncology, Department of Medicine and Department of Biochemistry & Molecular Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA
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Department of Population and Public Health Sciences, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA
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Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA
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Department of Radiology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA
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Departments of Radiology and Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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RareCyte, Inc., Seattle, WA 98121, USA
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Clinical Sequencing Division, Thermo Fisher Scientific, San Francisco, CA 94080, USA
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Departments of Radiology and Urology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Dario Marchetti
Int. J. Mol. Sci. 2022, 23(5), 2571; https://doi.org/10.3390/ijms23052571
Received: 20 January 2022 / Revised: 16 February 2022 / Accepted: 18 February 2022 / Published: 25 February 2022
(This article belongs to the Special Issue Circulating Tumor Cells: From Research to Therapeutic Application)
Integrating liquid biopsies of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) with other minimally invasive measures may yield more comprehensive disease profiles. We evaluated the feasibility of concurrent cellular and molecular analysis of CTCs and cfDNA combined with radiomic analysis of CT scans from patients with metastatic castration-resistant PC (mCRPC). CTCs from 22 patients were enumerated, stained for PC-relevant markers, and clustered based on morphometric and immunofluorescent features using machine learning. DNA from single CTCs, matched cfDNA, and buffy coats was sequenced using a targeted amplicon cancer hotspot panel. Radiomic analysis was performed on bone metastases identified on CT scans from the same patients. CTCs were detected in 77% of patients and clustered reproducibly. cfDNA sequencing had high sensitivity (98.8%) for germline variants compared to WBC. Shared and unique somatic variants in PC-related genes were detected in cfDNA in 45% of patients (MAF > 0.1%) and in CTCs in 92% of patients (MAF > 10%). Radiomic analysis identified a signature that strongly correlated with CTC count and plasma cfDNA level. Integration of cellular, molecular, and radiomic data in a multi-parametric approach is feasible, yielding complementary profiles that may enable more comprehensive non-invasive disease modeling and prediction. View Full-Text
Keywords: metastatic prostate cancer; cell-free DNA; circulating tumor cells; radiomics metastatic prostate cancer; cell-free DNA; circulating tumor cells; radiomics
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MDPI and ACS Style

Morrison, G.; Buckley, J.; Ostrow, D.; Varghese, B.; Cen, S.Y.; Werbin, J.; Ericson, N.; Cunha, A.; Lu, Y.-T.; George, T.; Smith, J.; Quinn, D.; Duddalwar, V.; Triche, T.; Goldkorn, A. Non-Invasive Profiling of Advanced Prostate Cancer via Multi-Parametric Liquid Biopsy and Radiomic Analysis. Int. J. Mol. Sci. 2022, 23, 2571. https://doi.org/10.3390/ijms23052571

AMA Style

Morrison G, Buckley J, Ostrow D, Varghese B, Cen SY, Werbin J, Ericson N, Cunha A, Lu Y-T, George T, Smith J, Quinn D, Duddalwar V, Triche T, Goldkorn A. Non-Invasive Profiling of Advanced Prostate Cancer via Multi-Parametric Liquid Biopsy and Radiomic Analysis. International Journal of Molecular Sciences. 2022; 23(5):2571. https://doi.org/10.3390/ijms23052571

Chicago/Turabian Style

Morrison, Gareth, Jonathan Buckley, Dejerianne Ostrow, Bino Varghese, Steven Y. Cen, Jeffrey Werbin, Nolan Ericson, Alexander Cunha, Yi-Tsung Lu, Thaddeus George, Jeffrey Smith, David Quinn, Vinay Duddalwar, Timothy Triche, and Amir Goldkorn. 2022. "Non-Invasive Profiling of Advanced Prostate Cancer via Multi-Parametric Liquid Biopsy and Radiomic Analysis" International Journal of Molecular Sciences 23, no. 5: 2571. https://doi.org/10.3390/ijms23052571

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