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

Colleen N. Biggs, Khurram M. Siddiqui, Ali A. Al-Zahrani, Siddika Pardhan, Sabine I. Brett, Qiu Q. Guo, Jun Yang, Philipp Wolf, Nicholas E. Power, Paul N. Durfee, Connor D. MacMillan, Jason L. Townson, Jeffrey C. Brinker, Neil E. Fleshner, Jonathan I. Izawa, Ann F. Chambers, Joseph L. Chin, Hon S. Leong

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)8839-8849
Number of pages11
JournalOncotarget
Volume7
Issue number8
DOIs
Publication statusPublished - 2016

Fingerprint

Prostate
Prostatic Neoplasms
Flow Cytometry
Biopsy
Neoplasm Grading
Prostatectomy
Extracellular Vesicles
Castration
Prostatic Hyperplasia
Healthy Volunteers

Keywords

  • Extracellular vesicles
  • Liquid biopsy
  • Nanoscale flow cytometry
  • Prostate cancer
  • Prostate microparticles

ASJC Scopus subject areas

  • Oncology

Cite this

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

In: Oncotarget, Vol. 7, No. 8, 2016, p. 8839-8849.

Research output: Contribution to journalArticle

Biggs, CN, Siddiqui, KM, Al-Zahrani, AA, Pardhan, S, Brett, SI, Guo, QQ, Yang, J, Wolf, P, Power, NE, Durfee, PN, MacMillan, CD, Townson, JL, Brinker, JC, Fleshner, NE, Izawa, JI, Chambers, AF, Chin, JL & Leong, HS 2016, 'Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry', Oncotarget, vol. 7, no. 8, pp. 8839-8849. https://doi.org/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. In: Oncotarget. 2016 ; Vol. 7, No. 8. pp. 8839-8849.
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AU - Biggs, Colleen N.

AU - Siddiqui, Khurram M.

AU - Al-Zahrani, Ali A.

AU - Pardhan, Siddika

AU - Brett, Sabine I.

AU - Guo, Qiu Q.

AU - Yang, Jun

AU - Wolf, Philipp

AU - Power, Nicholas E.

AU - Durfee, Paul N.

AU - MacMillan, Connor D.

AU - Townson, Jason L.

AU - Brinker, Jeffrey C.

AU - Fleshner, Neil E.

AU - Izawa, Jonathan I.

AU - Chambers, Ann F.

AU - Chin, Joseph L.

AU - Leong, Hon S.

PY - 2016

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N2 - 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.

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KW - Extracellular vesicles

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KW - Nanoscale flow cytometry

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