Increased Plasmatic Levels of PSA-Expressing Exosomes Distinguish Prostate Cancer Patients from Benign Prostatic Hyperplasia: A Prospective Study

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Prostate Specific Antigen (PSA) fails to discriminate between benign prostatic hyperplasia (BPH) and Prostate Cancer (PCa), resulting in large numbers of unnecessary biopsies and missed cancer diagnoses. Nanovesicles called exosomes are directly detectable in patient plasma and here we explore the potential use of plasmatic exosomes expressing PSA (Exo-PSA) in distinguishing healthy individuals, BPH, and PCa. Exosomes were obtained from plasma samples of 80 PCa, 80 BPH, and 80 healthy donors (CTR). Nanoparticle Tracking Analysis (NTA), immunocapture-based ELISA (IC-ELISA), and nanoscale flow-cytometry (NSFC), were exploited to detect and characterize plasmatic exosomes. Statistical analysis showed that plasmatic exosomes expressing both CD81 and PSA were significantly higher in PCa as compared to both BPH and CTR, reaching 100% specificity and sensitivity in distinguishing PCa patients from healthy individuals. IC-ELISA, NSFC, and Exo-PSA consensus score (EXOMIX) showed 98% to 100% specificity and sensitivity for BPH-PCa discrimination. This study outperforms the conventional PSA test with a minimally invasive widely exploitable approach.

Related collections

Most cited references 15

Record: found
Abstract: found
Article: not found

The meaning and use of the area under a receiver operating characteristic (ROC) curve.

J A Hanley, B J McNeil, Marnix van Holsbeeck (1982)

A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed ROC curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques.

0 comments Cited 3956 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Mortality results from a randomized prostate-cancer screening trial.

Gerald Andriole, E David Crawford, Robert L Grubb … (2009)

The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality. From 1993 through 2001, we randomly assigned 76,693 men at 10 U.S. study centers to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained. In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings. After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups. (ClinicalTrials.gov number, NCT00002540.) 2009 Massachusetts Medical Society

0 comments Cited 556 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Measurement of prostate-specific antigen in serum as a screening test for prostate cancer.

W Catalona, D S Smith, T Ratliff … (1991)

Prostate-specific antigen (PSA) is secreted exclusively by prostatic epithelial cells, and its serum concentration is increased in men with prostatic disease, including cancer. We evaluated its usefulness in the detection and staging of prostate cancer. We measured serum PSA concentrations in 1653 healthy men 50 or more years old. Those with PSA values greater than or equal to 4.0 micrograms per liter then underwent rectal examination and prostatic ultrasonography. Ultrasound-directed prostatic needle biopsies were performed in the men with abnormal findings on rectal examination, ultrasonography, or both. The results were compared with those in 300 consecutively studied men 50 or more years old who underwent ultrasound-directed biopsy because of symptoms or abnormal findings on rectal examination. Serum PSA levels ranged from 4.0 to 9.9 micrograms per liter in 6.5 percent of the 1653 men (107). Nineteen of the 85 men in this group (22 percent) who had prostatic biopsies had prostate cancer. Serum PSA levels were 10.0 micrograms per liter or higher in 1.8 percent of the 1653 men (30). Eighteen of the 27 men in this group (67 percent) who had prostatic biopsies had cancer. If rectal examination alone had been used to screen the men who had biopsies, 12 of the 37 cancers (32 percent) would have been missed. If ultrasonography alone had been used to screen these men, 16 of the 37 cancers (43 percent) would have been missed. Serum PSA measurement had the lowest error rate of the tests, and PSA measurement plus rectal examination had the lowest error rate of the two-test combinations. The combination of measurement of the serum PSA concentration and rectal examination, with ultrasonography performed in patients with abnormal findings, provides a better method of detecting prostate cancer than rectal examination alone.

0 comments Cited 238 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Cancers (Basel)

Journal ID (iso-abbrev): Cancers (Basel)

Journal ID (publisher-id): cancers

Title: Cancers

Publisher: MDPI

ISSN (Electronic): 2072-6694

Publication date (Electronic): 27 September 2019

Publication date Collection: October 2019

Volume: 11

Issue: 10

Electronic Location Identifier: 1449

Affiliations

[1 ]Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; mariantonia.logozzi@ 123456iss.it (M.L.); davide.mizzoni@ 123456iss.it (D.M.); rossella.diraimo@ 123456iss.it (R.D.R.)

[2 ]Neuroimmunology Unit, IRCCS Santa Lucia Foundation, 00179 Rome, Italy; df.angelini@ 123456hsantalucia.it (D.F.A.); g.borsellino@ 123456hsantalucia.it (G.B.); l.battistini@ 123456hsantalucia.it (L.B.)

[3 ]Environment and Health Department Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; alessandro.giuliani@ 123456iss.it

[4 ]Department of Urology, Policlinico Umberto I, Università La Sapienza, Viale dell’Università 33, 00161 Rome, Italy; martina.maggi@ 123456uniroma1.it (M.M.); alegenti@ 123456yahoo.com (A.G.); v.marzio89@ 123456gmail.com (V.M.); stefano.salciccia@ 123456uniroma1.it (S.S.); alessandro.sciarra@ 123456uniroma1.it (A.S.)

Author notes

[* ]Correspondence: stefano.fais@ 123456iss.it ; Tel.: +39-0649903195; Fax: +39-0649902436

Author information

Daniela F. Angelini https://orcid.org/0000-0003-4552-9226

Alessandro Giuliani https://orcid.org/0000-0002-4640-804X

Luca Battistini https://orcid.org/0000-0002-6488-4891

Article

Publisher ID: cancers-11-01449

DOI: 10.3390/cancers11101449

PMC ID: 6826376

PubMed ID: 31569672

SO-VID: a2d6d616-1e87-4c5b-a1d1-29ccc4516cb0

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Increased Plasmatic Levels of PSA-Expressing Exosomes Distinguish Prostate Cancer Patients from Benign Prostatic Hyperplasia: A Prospective Study

Read this article at

Abstract

Related collections

Cancer Metabolism

Most cited references 15

The meaning and use of the area under a receiver operating characteristic (ROC) curve.

Mortality results from a randomized prostate-cancer screening trial.

Measurement of prostate-specific antigen in serum as a screening test for prostate cancer.

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Categories

Comments

Comment on this article

Similar content 315

Cited by 42

Most referenced authors 2,174