CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Portugal.
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.
Biochimie. 2018 Dec;155:37-49. doi: 10.1016/j.biochi.2018.05.007. Epub 2018 May 18.
The identification of circulating biomarkers capable of being used as routine for diagnosis, prognosis, risk stratification and therapeutic monitoring is still the major aim at clinical proteomics. However, the direct search in blood samples or other clinical relevant biofluids is frequently associated with technical limitations that make the biomarker discovery process extremely difficult when using these types of samples. In this sense, the use of different approaches, such as the analysis of cells' secretomes, can be an important and promising complementary method for the identification and pre-selection of potential circulating biomarkers. Therefore, the present review is focused on published works exclusively devoted to the use of cells' secretomes for the identification of new circulating biomarkers. Considering these publications, the translational workflow used to identify potential protein circulating biomarkers from untargeted cells' secretome screenings is presented and discussed in this review. This translational workflow follows a 3-phase pipeline (discovery, verification and validation phase) similar to the "triangular strategy" already applied in biomarker discovery using blood or other clinical samples. For each phase it will be indicated the type of samples, the techniques used to analyze the samples, as well as, the major outcomes and methods used to analyze the data obtained. The examples presented in this review points out the potential of this secretome-based translational pipeline for the identification of new circulating biomarker candidates, with some of the biomarkers pointed out presenting better discriminatory capacity or at least improving the discriminatory capacity of well-established biomarkers. Finally, some of the potential improvements are also identified and discussed in this review, which can increase the visibility and importance of this cells' secretome-based pipeline for the identification of new potential circulating biomarkers.
鉴定能够常规用于诊断、预后、风险分层和治疗监测的循环生物标志物仍然是临床蛋白质组学的主要目标。然而，直接在血液样本或其他临床相关生物流体中进行搜索通常会受到技术限制的影响，这使得使用这些类型的样本进行生物标志物发现过程变得极其困难。在这种意义上，使用不同的方法，如细胞分泌组的分析，可以是鉴定和预选潜在循环生物标志物的重要和有前途的补充方法。因此，本综述专门侧重于发表的关于使用细胞分泌组鉴定新的循环生物标志物的工作。考虑到这些出版物，本综述介绍并讨论了用于从无目标细胞分泌组筛选中鉴定潜在蛋白循环生物标志物的转化工作流程。该转化工作流程遵循类似于已应用于使用血液或其他临床样本进行生物标志物发现的“三角策略”的 3 个阶段管道（发现、验证和验证阶段）。对于每个阶段，将指出样本的类型、用于分析样本的技术，以及用于分析获得的数据的主要结果和方法。本综述中提出的示例指出了基于分泌组的这种转化管道用于鉴定新的循环生物标志物候选物的潜力，其中一些指出的生物标志物具有更好的区分能力，或者至少提高了既定生物标志物的区分能力。最后，本综述还确定并讨论了一些潜在的改进措施，这可以提高这种基于细胞分泌组的管道用于鉴定新的潜在循环生物标志物的可见度和重要性。
