Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer.
Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer.
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DOI：
10.1371/journal.pone.0046737
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wall NR
中科院分区：
文献类型：
--
作者：
Khan S;Jutzy JM;Valenzuela MM;Turay D;Aspe JR;Ashok A;Mirshahidi S;Mercola D;Lilly MB;Wall NR
Survivin在前列腺癌（PCa）中表达，并且其下调使PCa细胞在体外和体内对化疗剂敏感。被称为外泌体的小的膜结合囊泡，从内体膜隔室分泌，含有RNA和蛋白质，它们容易通过外泌体内化转运到受体细胞中。近年来的研究表明，肿瘤源性外泌体在肿瘤的生长和转移中发挥着多种作用，并可能通过免疫逃逸、肿瘤侵袭和血管生成等途径发挥这些作用。此外，外泌体分析可以提供新的生物标志物来诊断或监测PCa治疗。使用超离心法从来自39名PCa患者、20名BPH患者、8名前列腺癌复发者和16名健康对照的血浆和血清中纯化外泌体，并且分别使用ELISA和Western印迹法从血浆和纯化的外泌体中定量和可视化它们的量和质量。与来自BPH和对照的那些相比，存活素在肿瘤来源的样品中显著增加，在从新诊断的表现出低（6）或高（9）Gleason评分的患者收集的外来体中检测到的存活素的量几乎没有差异。与对照组相比，化疗复发患者的外泌体Survivin水平也更高。这些研究表明，Survivin存在于来自正常、BPH和PCa受试者的血浆外泌体中。外泌体Survivin在PCa血浆中的相对量显著高于炎症前BPH和对照血浆。外泌体Survivin的这种差异表达见于新诊断的和晚期的患有高或低级别癌症的PCa受试者。血浆外泌体存活素水平的分析可以提供用于诊断或监测PCa的方便工具，并且由于其在低以及高Gleason评分的样品中升高，因此可以用于早期检测。
Survivin is expressed in prostate cancer (PCa), and its downregulation sensitizes PCa cells to chemotherapeutic agents in vitro and in vivo. Small membrane-bound vesicles called exosomes, secreted from the endosomal membrane compartment, contain RNA and protein that they readily transport via exosome internalization into recipient cells. Recent progress has shown that tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions via immune escape, tumor invasion and angiogenesis. Furthermore, exosome analysis may provide novel biomarkers to diagnose or monitor PCa treatment. Exosomes were purified from the plasma and serum from 39 PCa patients, 20 BPH patients, 8 prostate cancer recurrent and 16 healthy controls using ultracentrifugation and their quantities and qualities were quantified and visualized from both the plasma and the purified exosomes using ELISA and Western blotting, respectively. Survivin was significantly increased in the tumor-derived samples, compared to those from BPH and controls with virtually no difference in the quantity of Survivin detected in exosomes collected from newly diagnosed patients exhibiting low (six) or high (nine) Gleason scores. Exosome Survivin levels were also higher in patients that had relapsed on chemotherapy compared to controls. These studies demonstrate that Survivin exists in plasma exosomes from both normal, BPH and PCa subjects. The relative amounts of exosomal Survivin in PCa plasma was significantly higher than in those with pre-inflammatory BPH and control plasma. This differential expression of exosomal Survivin was seen with both newly diagnosed and advanced PCa subjects with high or low-grade cancers. Analysis of plasma exosomal Survivin levels may offer a convenient tool for diagnosing or monitoring PCa and may, as it is elevated in low as well as high Gleason scored samples, be used for early detection.
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