PDF(Pubmed)
Abstract：
Urinary extracellular vesicles (uEVs) are enriched with glycosylated proteins which have been extensively studied as putative biomarkers of urological cancers. Here, we characterized the glycosylation and integrin profile of EVs derived from urological cancer cell lines. We used fluorescent europium-doped nanoparticles coated with lectins and antibodies to identify a biomarker combination consisting of integrin subunit alpha 3 (ITGA3) and fucose. In addition, we used the same cancer cell line-derived EVs as analytical standards to assess the sensitivity of the ITGA3-UEA assay. The clinical performance of the ITGA3-UEA assay was analysed using urine samples of various urological pathologies including diagnostically challenging benign prostatic hyperplasia (BPH), prostate cancer (PCa) and bladder cancer (BlCa). The assay can significantly discriminate BlCa from all other patient groups: PCa (9.2-fold; p = 0.00038), BPH (5.5-fold; p = 0.004) and healthy individuals (and 23-fold; p = 0.0001). Our results demonstrate that aberrantly fucosylated uEVs and integrin ITGA3 can be detected with fucose-specific lectin UEA in a simple bioaffinity assay for the detection of BlCa directly from unprocessed urine.
摘要：
尿细胞外囊泡（uEV）富含糖基化蛋白，已被广泛研究为泌尿系癌症的推定生物标志物。这里,我们表征了源自泌尿系癌细胞系的EV的糖基化和整合素谱。我们使用涂覆有凝集素和抗体的荧光铕掺杂纳米颗粒来鉴定由整联蛋白亚基α3（ITGA3）和岩藻糖组成的生物标志物组合。此外,我们使用相同的癌细胞系来源的EV作为分析标准来评估ITGA3-UEA测定的灵敏度.ITGA3-UEA分析的临床表现使用各种泌尿系统病理的尿样分析，包括诊断挑战性良性前列腺增生（BPH），前列腺癌（PCa）和膀胱癌（BlCa）。该测定法可以显着区分所有其他患者组的BlCa：PCa（9.2倍；p=0.00038），BPH(5.5倍;p=0.004)和健康个体(和23倍;p=0.0001)。我们的结果表明，在简单的生物亲和测定法中，可以用岩藻糖特异性凝集素UEA检测异常岩藻糖基化的uEV和整联蛋白ITGA3，以直接从未加工的尿液中检测BlCa。
