RPPA Unit, Proteomics Area, Core Facilities, Istituto Superiore di Sanità, Rome, Italy.
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Cell Death Dis. 2021 Jun 21;12(7):636. doi: 10.1038/s41419-021-03909-z.
Extracellular vesicles (EVs) and their cargo represent an intriguing source of cancer biomarkers for developing robust and sensitive molecular tests by liquid biopsy. Prostate cancer (PCa) is still one of the most frequent and deadly tumor in men and analysis of EVs from biological fluids of PCa patients has proven the feasibility and the unprecedented potential of such an approach. Here, we exploited an antibody-based proteomic technology, i.e. the Reverse-Phase Protein microArrays (RPPA), to measure key antigens and activated signaling in EVs isolated from sera of PCa patients. Notably, we found tumor-specific protein profiles associated with clinical settings as well as candidate markers for EV-based tumor diagnosis. Among others, PD-L1, ERG, Integrin-β5, Survivin, TGF-β, phosphorylated-TSC2 as well as partners of the MAP-kinase and mTOR pathways emerged as differentially expressed endpoints in tumor-derived EVs. In addition, the retrospective analysis of EVs from a 15-year follow-up cohort generated a protein signature with prognostic significance. Our results confirm that serum-derived EV cargo may be exploited to improve the current diagnostic procedures while providing potential prognostic and predictive information. The approach proposed here has been already applied to tumor entities other than PCa, thus proving its value in translational medicine and paving the way to innovative, clinically meaningful tools.
细胞外囊泡（EVs）及其携带物代表了一个有趣的癌症生物标志物来源，可用于开发强大而敏感的液体活检分子检测。前列腺癌（PCa）仍然是男性中最常见和最致命的肿瘤之一，对来自 PCa 患者生物体液的 EVs 的分析已经证明了这种方法的可行性和前所未有的潜力。在这里，我们利用了一种基于抗体的蛋白质组学技术，即反相蛋白微阵列（RPPA），来测量从 PCa 患者血清中分离出的 EV 中的关键抗原和激活的信号。值得注意的是，我们发现了与临床情况相关的肿瘤特异性蛋白图谱，以及用于 EV 为基础的肿瘤诊断的候选标志物。除其他外，PD-L1、ERG、整合素-β5、Survivin、TGF-β、磷酸化 TSC2 以及 MAP 激酶和 mTOR 通路的伙伴在肿瘤衍生的 EVs 中表现出差异表达的终点。此外，对来自 15 年随访队列的 EVs 的回顾性分析生成了具有预后意义的蛋白质特征。我们的结果证实，血清衍生的 EV 携带物可用于改善当前的诊断程序，同时提供潜在的预后和预测信息。这里提出的方法已经应用于除 PCa 以外的肿瘤实体，从而证明了其在转化医学中的价值，并为创新的、具有临床意义的工具铺平了道路。
