Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Expert Rev Proteomics. 2010 Dec;7(6):879-95. doi: 10.1586/epr.10.81.
The early detection of colorectal cancer is one of the great challenges in the battle against this disease. However, owing to its heterogeneous character, single markers are not likely to provide sufficient diagnostic power to be used in colorectal cancer population screens. This review provides an overview of recent studies aimed at the discovery of new diagnostic protein markers through proteomics-based approaches. It indicates that studies that start with the proteomic analysis of tumor tissue or tumor cell lines (near the source) have a high potential to yield novel and colorectal cancer-specific biomarkers. In the next step, the diagnostic accuracy of these candidate markers can be assessed by a targeted ELISA assay using serum from colorectal cancer patients and healthy controls. Instead, direct proteomic analysis of serum yields predominantly secondary markers composed of fragments of abundant serum proteins that may be associated with tumor-associated protease activity, and alternatively, immunoproteomic analysis of the serum antibody repertoire provides a valuable tool to identify the molecular imprint of colorectal cancer-associated antigens directly from patient serum samples. The latter approach also allows a relatively easy translation into targeted assays. Eventually, multimarker assays should be developed to reach a diagnostic accuracy that meets the stringent criteria for colorectal cancer screening at the population level.
结直肠癌的早期检测是对抗这种疾病的重大挑战之一。然而，由于其异质性，单一标志物不太可能提供足够的诊断能力，无法用于结直肠癌人群筛查。本文综述了最近通过基于蛋白质组学的方法发现新的诊断蛋白标志物的研究。结果表明，从肿瘤组织或肿瘤细胞系（接近源头）的蛋白质组学分析开始的研究具有很高的潜力，可以产生新的、结直肠癌特异性的生物标志物。在下一步中，可以使用来自结直肠癌患者和健康对照者的血清通过靶向 ELISA 测定来评估这些候选标志物的诊断准确性。相反，血清的直接蛋白质组学分析主要产生由丰富的血清蛋白片段组成的次要标志物，这些片段可能与肿瘤相关的蛋白酶活性有关，或者，对血清抗体库进行免疫蛋白质组学分析提供了一种有价值的工具，可以直接从患者的血清样本中识别结直肠癌相关抗原的分子印记。后一种方法还允许相对容易地转化为靶向测定。最终，应开发多标志物测定法以达到满足人群结直肠癌筛查严格标准的诊断准确性。
