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

Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer
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DOI:
10.1038/srep30386
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发表时间:
2016-08-09
期刊:
影响因子:
4.6
通讯作者:
Lee, Ji Youl
Lee, Ji Youl
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Park, Yong Hyun;Shin, Hyun Woo;Lee, Ji Youl

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细胞外囊泡(EV)可能在癌症的发生和发展中起重要作用。我们旨在研究前列腺癌(PCa)患者中前列腺特异性EV的预后潜力。血浆和前列腺组织收集自接受PCa(n = 82)或良性前列腺增生(BPH,n = 28)手术的患者。为了分析前列腺中EV的数量,我们进行了透射电子显微镜(TEM),CD 63和前列腺特异性膜抗原(PSMA)的免疫TEM和免疫荧光染色。从血浆中分离EV后,使用ELISA试剂盒测量CD 63和PSMA浓度。前列腺PSMA阳性区域在BPH和低、中、高危PCa患者中存在差异(2.4、8.2、17.5、26.5%,p < 0.001)。血浆PSMA阳性EV浓度在BPH和低、中和高风险PCa患者中不同(21.9、43.4、49.2、59.9 ng/mL,p < 0.001),ROC曲线分析表明血浆PSMA阳性EV浓度区分PCa和BPH(AUC 0.943)。血浆PSMA阳性EV浓度较低的患者具有较大的前列腺体积(50.2对33.4 cc,p < 0.001)和较低的病理学Gleason评分(p = 0.025)。在18个月的中位随访期间,血浆PSMA阳性EV浓度较低的患者比前列腺特异性EV水平较高的患者发生生化衰竭的风险更低(p = 0.085)。
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).