Atlantic Cancer Research Institute, Moncton, NB, Canada.
Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada.
Sci Rep. 2023 Jun 7;13(1):9251. doi: 10.1038/s41598-023-36370-3.
Pancreatic ductal adenocarcinoma (PDAC) has a high fatality rate, mainly due to its asymptomatic nature until late-stage disease and therefore delayed diagnosis that leads to a lack of timely treatment intervention. Consequently, there is a significant need for better methods to screen populations that are at high risk of developing PDAC. Such advances would result in earlier diagnosis, more treatment options, and ultimately better outcomes for patients. Several recent studies have applied the concept of liquid biopsy, which is the sampling of a biofluid (such as blood plasma) for the presence of disease biomarkers, to develop screening approaches for PDAC; several of these studies have focused on analysis of extracellular vesicles (EVs) and their cargoes. While these studies have identified many potential biomarkers for PDAC that are present within EVs, their application to clinical practice is hindered by the lack of a robust, reproducible method for EV isolation and analysis that is amenable to a clinical setting. Our previous research has shown that the Vn96 synthetic peptide is indeed a robust and reproducible method for EV isolation that has the potential to be used in a clinical setting. We have therefore chosen to investigate the utility of the Vn96 synthetic peptide for this isolation of EVs from human plasma and the subsequent detection of small RNA biomarkers of PDAC by Next-generation sequencing (NGS) analysis. We find that analysis of small RNA from Vn96-isolated EVs permits the discrimination of PDAC patients from non-affected individuals. Moreover, analyses of all small RNA species, miRNAs, and lncRNA fragments are most effective at segregating PDAC patients from non-affected individuals. Several of the identified small RNA biomarkers have been previously associated with and/or characterized in PDAC, indicating the validity of our findings, whereas other identified small RNA biomarkers may have novel roles in PDAC or cancer in general. Overall, our results provide a basis for a clinically-amendable detection and/or screening strategy for PDAC using a liquid biopsy approach that relies on Vn96-mediated isolation of EVs from plasma.
胰腺导管腺癌 (PDAC) 死亡率很高，主要是因为其在疾病晚期之前无症状，因此诊断延迟导致缺乏及时的治疗干预。因此，非常需要更好的方法来筛选患有 PDAC 风险较高的人群。这些进展将导致更早的诊断、更多的治疗选择，并最终为患者带来更好的结果。最近的几项研究应用了液体活检的概念，即从生物体液（如血浆）中采样以寻找疾病生物标志物，从而开发 PDAC 的筛查方法；其中一些研究集中在分析细胞外囊泡 (EVs) 及其 cargo。虽然这些研究已经确定了许多存在于 EVs 中的 PDAC 潜在生物标志物，但由于缺乏适用于临床环境的稳健、可重复的 EV 分离和分析方法，它们在临床实践中的应用受到阻碍。我们之前的研究表明，Vn96 合成肽确实是一种稳健且可重复的 EV 分离方法，具有在临床环境中使用的潜力。因此，我们选择研究 Vn96 合成肽在从人血浆中分离 EV 以及随后通过下一代测序 (NGS) 分析检测 PDAC 的小 RNA 生物标志物方面的应用。我们发现，分析 Vn96 分离的 EV 中的小 RNA 可以区分 PDAC 患者和非患者。此外，对所有小 RNA 物种、miRNA 和 lncRNA 片段的分析最有效地将 PDAC 患者与非患者区分开来。一些鉴定出的小 RNA 生物标志物以前与 PDAC 相关联和/或在 PDAC 中进行了特征描述，这表明我们的研究结果是有效的，而其他鉴定出的小 RNA 生物标志物可能在 PDAC 或一般癌症中具有新的作用。总的来说，我们的研究结果为使用液体活检方法通过 Vn96 介导的从血浆中分离 EV 来检测和/或筛查 PDAC 提供了一个临床可修改的基础。
