Dataset Information

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

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.

SUBMITTER: Logozzi M

PROVIDER: S-EPMC6826376 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Logozzi Mariantonia M Angelini Daniela F DF Giuliani Alessandro A Mizzoni Davide D Di Raimo Rossella R Maggi Martina M Gentilucci Alessandro A Marzio Vittorio V Salciccia Stefano S Borsellino Giovanna G Battistini Luca L Sciarra Alessandro A Fais Stefano S

Cancers 20190927 10

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 (CT ...[more]

PMID: 31569672

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Project description:BackgroundProstate Cancer (PCa) represents the second leading cause of cancer-related death in men. Prostate-specific antigen (PSA) serum testing, currently used for PCa screening, lacks the necessary sensitivity and specificity. New non-invasive diagnostic tools able to discriminate tumoral from benign conditions and aggressive (AG-PCa) from indolent forms of PCa (NAG-PCa) are required to avoid unnecessary biopsies.MethodsIn this work, 32 formerly N-glycosylated peptides were quantified by PRM (parallel reaction monitoring) in 163 serum samples (79 from PCa patients and 84 from individuals affected by benign prostatic hyperplasia (BPH)) in two technical replicates. These potential biomarker candidates were prioritized through a multi-stage biomarker discovery pipeline articulated in: discovery, LC-PRM assay development and verification phases. Because of the well-established involvement of glycoproteins in cancer development and progression, the proteomic analysis was focused on glycoproteins enriched by TiO2 (titanium dioxide) strategy.ResultsMachine learning algorithms have been applied to the combined matrix comprising proteomic and clinical variables, resulting in a predictive model based on six proteomic variables (RNASE1, LAMP2, LUM, MASP1, NCAM1, GPLD1) and five clinical variables (prostate dimension, proPSA, free-PSA, total-PSA, free/total-PSA) able to distinguish PCa from BPH with an area under the Receiver Operating Characteristic (ROC) curve of 0.93. This model outperformed PSA alone which, on the same sample set, was able to discriminate PCa from BPH with an AUC of 0.79. To improve the clinical managing of PCa patients, an explorative small-scale analysis (79 samples) aimed at distinguishing AG-PCa from NAG-PCa was conducted. A predictor of PCa aggressiveness based on the combination of 7 proteomic variables (FCN3, LGALS3BP, AZU1, C6, LAMB1, CHL1, POSTN) and proPSA was developed (AUC of 0.69).ConclusionsTo address the impelling need of more sensitive and specific serum diagnostic tests, a predictive model combining proteomic and clinical variables was developed. A preliminary evaluation to build a new tool able to discriminate aggressive presentations of PCa from tumors with benign behavior was exploited. This predictor displayed moderate performances, but no conclusions can be drawn due to the limited number of the sample cohort. Data are available via ProteomeXchange with identifier PXD035935.

Dataset Information

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

Publications

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

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