Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer - PubMed (original) (raw)

Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer

Yong Hyun Park et al. Sci Rep. 2016.

Erratum in

Abstract

Extracellular vesicles (EVs) may play an important role in cancer development and progression. We aimed to investigate the prognostic potential of prostate-specific EVs in prostate cancer (PCa) patients. Plasma and prostate tissue were collected from patients who underwent surgery for PCa (n = 82) or benign prostatic hyperplasia (BPH, n = 28). To analyze the quantity of EVs in prostate, we performed transmission electron microscopy (TEM), immuno-TEM with CD63 and prostate-specific membrane antigen (PSMA), and immunofluorescence staining. After EV isolation from plasma, CD63 and PSMA concentration was measured using ELISA kits. PSMA-positive areas in prostate differed in patients with BPH, and low-, intermediate-, and high-risk PCa (2.4, 8.2, 17.5, 26.5%, p < 0.001). Plasma PSMA-positive EV concentration differed in patients with BPH, and low-, intermediate-, and high-risk PCa (21.9, 43.4, 49.2, 59.9 ng/mL, p < 0.001), and ROC curve analysis indicated that plasma PSMA-positive EV concentration differentiated PCa from BPH (AUC 0.943). Patients with lower plasma PSMA-positive EV concentration had greater prostate volume (50.2 vs. 33.4 cc, p < 0.001) and lower pathologic Gleason score (p = 0.025). During the median follow-up of 18 months, patients with lower plasma PSMA-positive EV concentration tended to have a lower risk of biochemical failure than those with higher levels of prostate-specific EVs (p = 0.085).

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Figures

Figure 1

Figure 1. Representative transmission electron miscroscopy (TEM) images of extracellular vesicles (EVs) in prostate tissue.

Vesicles 30–100 nm in diameter were observed by TEM. (A) Human benign prostatic hyperplasia (BPH) cells produce several microvesicles. The lower panel shows a magnified region of (A). The EVs appear as white dots (indicated by an arrow). (B) Human prostate cancer cells shed more microvesicles compared to BPH cells. The lower panel shows a magnified region of (B) Bars in low-magnification images, 1 μm. Bars in high-magnification images, 200 nm.

Figure 2

Figure 2

Representative TEM images of (A) immunoperoxidase/diaminobenzidine methods and (B) immunogold enhancement showing ultrastructural localization of PSMA. Bar in (A) 1 μm. Bar in (B) 10 nm.

Figure 3

Figure 3

Representative images of immunofluorescence staining for CD63 and PSMA in patients with (A) benign prostatic hyperplasia and (B) prostate cancer. (C) Quantification of PSMA-positive areas in prostatic tissue (p < 0.001).

Figure 4

Figure 4

Representative images of TEM with immunogold enhancement with anti-CD63 (A) and PSMA (B) antibodies. (C) Correlation between the plasma PSMA-positive EV concentration and PSMA-positive areas in prostatic tissue (Spearman’s rho correlation coefficient = 0.672, p < 0.001).

Figure 5

Figure 5

Quantification of the concentration of (A) plasma PSMA-positive EV (p < 0.001) and (B) plasma CD63-positive EV (p = 0.067).

Figure 6

Figure 6. Receiver operating characteristic curve analysis using plasma PSMA-positive EV concentration for discrimination of prostate cancer from benign prostatic hyperplasia.

Figure 7

Figure 7. Biochemical recurrence free-survival according to plasma PSMA-positive EV concentration (p = 0.085).

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