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Title: Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry

Abstract

Background: Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Patients and Methods: Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. Results: PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a highrisk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection ofmore » the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. Conclusions: PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.« less

Authors:
 [1];  [1];  [2];  [1];  [1];  [3];  [3];  [4];  [5];  [6];  [1];  [6];  [7];  [8];  [5];  [9];  [5];  [1]
  1. Western Univ., London (Canada). Dept. of Surgery; Lawson Health Research Inst., London (Canada). Translational Prostate Cancer Research Lab.
  2. Western Univ., London (Canada). Dept. of Surgery; Lawson Health Research Inst., London (Canada). Translational Prostate Cancer Research Lab.; Univ. of Damman (Saudi Arabia). Dept. of Urology
  3. Western Univ., London (Canada). Dept. of Mechanical and Materials Engineering
  4. Univ. Medical Center Freiburg (Germany). Dept. of Urology
  5. Western Univ., London (Canada). Dept. of Surgery; Western Univ., London (Canada). Dept. of Oncology; Lawson Health Research Inst., London (Canada). Translational Prostate Cancer Research Lab.
  6. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
  7. Sandia National Laboratories, Albuquerque, NM, USA
  8. Univ. of Toronto, ON (Canada). Univ. Health Network
  9. Western Univ., London (Canada). Dept. of Oncology
Publication Date:
Research Org.:
Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1627990
Grant/Contract Number:  
NA0003525
Resource Type:
Accepted Manuscript
Journal Name:
Oncotarget
Additional Journal Information:
Journal Volume: 7; Journal Issue: 8; Journal ID: ISSN 1949-2553
Publisher:
Impact Journals
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Oncology; Cell Biology

Citation Formats

Biggs, Colleen N., Siddiqui, Khurram M., Al-Zahrani, Ali A., Pardhan, Siddika, Brett, Sabine I., Guo, Qiu Q., Yang, Jun, Wolf, Philipp, Power, Nicholas E., Durfee, Paul N., MacMillan, Connor D., Townson, Jason L., Brinker, Jeffrey C., Fleshner, Neil E., Izawa, Jonathan I., Chambers, Ann F., Chin, Joseph L., and Leong, Hon S. Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry. United States: N. p., 2016. Web. doi:10.18632/oncotarget.6983.
Biggs, Colleen N., Siddiqui, Khurram M., Al-Zahrani, Ali A., Pardhan, Siddika, Brett, Sabine I., Guo, Qiu Q., Yang, Jun, Wolf, Philipp, Power, Nicholas E., Durfee, Paul N., MacMillan, Connor D., Townson, Jason L., Brinker, Jeffrey C., Fleshner, Neil E., Izawa, Jonathan I., Chambers, Ann F., Chin, Joseph L., & Leong, Hon S. Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry. United States. doi:10.18632/oncotarget.6983.
Biggs, Colleen N., Siddiqui, Khurram M., Al-Zahrani, Ali A., Pardhan, Siddika, Brett, Sabine I., Guo, Qiu Q., Yang, Jun, Wolf, Philipp, Power, Nicholas E., Durfee, Paul N., MacMillan, Connor D., Townson, Jason L., Brinker, Jeffrey C., Fleshner, Neil E., Izawa, Jonathan I., Chambers, Ann F., Chin, Joseph L., and Leong, Hon S. Fri . "Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry". United States. doi:10.18632/oncotarget.6983. https://www.osti.gov/servlets/purl/1627990.
@article{osti_1627990,
title = {Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry},
author = {Biggs, Colleen N. and Siddiqui, Khurram M. and Al-Zahrani, Ali A. and Pardhan, Siddika and Brett, Sabine I. and Guo, Qiu Q. and Yang, Jun and Wolf, Philipp and Power, Nicholas E. and Durfee, Paul N. and MacMillan, Connor D. and Townson, Jason L. and Brinker, Jeffrey C. and Fleshner, Neil E. and Izawa, Jonathan I. and Chambers, Ann F. and Chin, Joseph L. and Leong, Hon S.},
abstractNote = {Background: Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Patients and Methods: Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. Results: PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a highrisk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. Conclusions: PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.},
doi = {10.18632/oncotarget.6983},
journal = {Oncotarget},
number = 8,
volume = 7,
place = {United States},
year = {2016},
month = {1}
}

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