外泌体前列腺特异性膜抗原（PSMA）和 caveolin-1 作为前列腺癌的潜在生物标志物-来自塞尔维亚人群的证据。

Exosomal Prostate-Specific Membrane Antigen (PSMA) and Caveolin-1 as Potential Biomarkers of Prostate Cancer-Evidence from Serbian Population.

机构信息

Centre for Human Molecular Genetics, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia.

Centre for Electrone Microscopy, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia.

出版信息

Int J Mol Sci. 2024 Mar 21;25(6):3533. doi: 10.3390/ijms25063533.

DOI:10.3390/ijms25063533

PMID:38542507

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10970688/

Abstract

Prostate-specific membrane antigen (PSMA) and caveolin-1 are membrane proteins that are overexpressed in prostate cancer (PCa) and are involved in tumor growth and increase in aggressiveness. The aim of the present study is therefore to evaluate PSMA and caveolin-1 proteins from plasma exosomes as effective liquid biopsy biomarkers for PCa. This study included 39 patients with PCa and 33 with benign prostatic hyperplasia (BPH). The shape and size of the exosomes were confirmed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analysis. Immunogold analysis showed that PSMA is localized to the membrane of exosomes isolated from the plasma of both groups of participants. The relative protein levels of PSMA and caveolin-1 in the plasma exosomes of PCa and BPH patients were determined by Western blot analysis. The relative level of the analyzed plasma exosomal proteins was compared between PCa and BPH patients and the relevance of the exosomal PSMA and caveoin-1 level to the clinicopathological parameters in PCa was investigated. The analysis performed showed an enrichment of exosomal PSMA in the plasma of PCa patients compared to the exosomes of men with BPH. The level of exosomal caveolin-1 in plasma was significantly higher in PCa patients with high PSA levels, clinical-stage T3 or T4 and in the group of PCa patients with aggressive PCa compared to favorable clinicopathological features or tumor aggressiveness. Plasma exosomes may serve as a suitable object for the identification of potential biomarkers for the early diagnosis and prognosis of PCa as well as carriers of therapeutic agents in precision medicine of PCa treatment.

摘要

前列腺特异性膜抗原（PSMA）和小窝蛋白-1 是在前列腺癌（PCa）中过度表达的膜蛋白，参与肿瘤生长和侵袭性增加。因此，本研究旨在评估来自血浆外泌体的 PSMA 和小窝蛋白-1 蛋白作为 PCa 的有效液体活检生物标志物。本研究纳入了 39 例 PCa 患者和 33 例良性前列腺增生（BPH）患者。通过透射电子显微镜（TEM）和扫描电子显微镜（SEM）分析确认了外泌体的形状和大小。免疫金分析显示，PSMA 定位于从两组参与者的血浆中分离的外泌体的膜上。通过 Western blot 分析确定了 PCa 和 BPH 患者血浆外泌体中 PSMA 和小窝蛋白-1 的相对蛋白水平。比较了 PCa 和 BPH 患者分析的血浆外泌体蛋白的相对水平，并研究了外泌体 PSMA 和小窝蛋白-1 水平与 PCa 临床病理参数的相关性。分析结果显示，与 BPH 患者的外泌体相比，PCa 患者的血浆中外泌体 PSMA 明显富集。在 PSA 水平较高、临床分期 T3 或 T4 以及侵袭性 PCa 患者组中，PCa 患者血浆中外泌体小窝蛋白-1 的水平明显高于具有良好临床病理特征或肿瘤侵袭性的患者。血浆外泌体可以作为鉴定 PCa 早期诊断和预后的潜在生物标志物以及 PCa 精准治疗中治疗剂载体的合适对象。