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Cell Line Secretome and Tumor Tissue Proteome Markers for Early Detection of Colorectal Cancer: A Systematic Review

机译:细胞系分泌蛋白和肿瘤组织蛋白质组学标记物用于大肠癌的早期检测:系统评价

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Objective: In order to find low abundant proteins secretome and tumor tissue proteome data have been explored in the last few years for the diagnosis of colorectal cancer (CRC). In this review we aim to summarize the results of studies evaluating markers derived from the secretome and tumor proteome for blood based detection of colorectal cancer. Methods: Observing the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines PubMed and Web of Science databases were searched systematically for relevant studies published up to 18 July 2017. After screening for predefined eligibility criteria a total of 47 studies were identified. Information on diagnostic performance indicators, methodological procedures and validation was extracted. Functions of proteins were identified from the UniProt database and the the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess study quality. Results: Forty seven studies meeting inclusion criteria were identified. Overall, 83 different proteins were identified, with carcinoembryonic Antigen (CEA) being by far the most commonly reported (reported in 24 studies). Evaluation of the markers or marker combinations in blood samples from CRC cases and controls yielded apparently very promising diagnostic performances, with area under the curve >0.9 in several cases, but lack of internal or external validation, overoptimism due to overfitting and spectrum bias due to evaluation in clinical setting rather than screening settings are major concerns. Conclusions: Secretome and tumor proteome-based biomarkers when validated in blood yield promising candidates. However, for discovered protein markers to be clinically applicable as screening tool they have to be specific for early stages and need to be validated externally in larger studies with participants recruited in true screening setting.
机译:目的:为寻找低丰度蛋白质,分泌蛋白质组和肿瘤组织蛋白质组学数据已在最近几年中用于诊断大肠癌(CRC)。在这篇综述中,我们旨在总结评估基于分泌组和肿瘤蛋白质组的标记物用于基于血液的大肠癌检测的研究结果。方法:观察系统评价和荟萃分析(PRISMA)指南的首选报告项目,系统搜索PubMed和Web of Science数据库以查找截至2017年7月18日发表的相关研究。筛选预定义的资格标准后,共鉴定出47项研究。提取了有关诊断性能指标,方法学程序和验证的信息。从UniProt数据库中鉴定出蛋白质的功能,并使用“诊断准确性研究2质量评估”(QUADAS-2)工具评估研究质量。结果:确定了47项符合纳入标准的研究。总体上,已鉴定出83种不同的蛋白质,其中癌胚抗原(CEA)是迄今为止最常报道的蛋白质(在24个研究中报告)。对来自CRC病例和对照的血样中的标记物或标记物组合的评估显然具有非常有前途的诊断性能,在某些情况下,曲线下面积> 0.9,但是缺乏内部或外部验证,由于过度拟合导致的过分乐观以及由于在临床环境而不是筛查环境中进行评估是主要关注的问题。结论:在血液中验证分泌蛋白和肿瘤蛋白质组学为基础的生物标志物后,有希望的候选物。但是,要使发现的蛋白质标记物在临床上可作为筛选工具,它们必须对早期阶段具有特异性,并且需要在真正的筛选条件下招募的参与者中进行更大范围的外部研究验证。

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