Boja Emily S, Rodriguez Henry
Office of Cancer Clinical Proteomics Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Korean J Lab Med. 2011 Apr;31(2):61-71. doi: 10.3343/kjlm.2011.31.2.61.
Better biomarkers are urgently needed to cancer detection, diagnosis, and prognosis. While the genomics community is making significant advances in understanding the molecular basis of disease, proteomics will delineate the functional units of a cell, proteins and their intricate interaction network and signaling pathways for the underlying disease. Great progress has been made to characterize thousands of proteins qualitatively and quantitatively in complex biological systems by utilizing multi-dimensional sample fractionation strategies, mass spectrometry and protein microarrays. Comparative/quantitative analysis of high-quality clinical biospecimen (e.g., tissue and biofluids) of human cancer proteome landscape has the potential to reveal protein/peptide biomarkers responsible for this disease by means of their altered levels of expression, post-translational modifications as well as different forms of protein variants. Despite technological advances in proteomics, major hurdles still exist in every step of the biomarker development pipeline. The National Cancer Institute's Clinical Proteomic Technologies for Cancer initiative (NCI-CPTC) has taken a critical step to close the gap between biomarker discovery and qualification by introducing a pre-clinical "verification" stage in the pipeline, partnering with clinical laboratory organizations to develop and implement common standards, and developing regulatory science documents with the US Food and Drug Administration to educate the proteomics community on analytical evaluation requirements for multiplex assays in order to ensure the safety and effectiveness of these tests for their intended use.
癌症检测、诊断和预后急需更好的生物标志物。虽然基因组学界在理解疾病的分子基础方面取得了重大进展，但蛋白质组学将描绘细胞的功能单元、蛋白质及其复杂的相互作用网络以及潜在疾病的信号通路。通过利用多维样品分级策略、质谱和蛋白质微阵列，在复杂生物系统中对数千种蛋白质进行定性和定量表征方面已经取得了很大进展。对人类癌症蛋白质组图谱的高质量临床生物标本（如组织和生物流体）进行比较/定量分析，有可能通过其表达水平的改变、翻译后修饰以及不同形式的蛋白质变体来揭示导致这种疾病的蛋白质/肽生物标志物。尽管蛋白质组学技术取得了进展，但在生物标志物开发流程的每一步仍然存在重大障碍。美国国立癌症研究所的癌症临床蛋白质组技术计划（NCI-CPTC）迈出了关键一步，通过在流程中引入临床前“验证”阶段、与临床实验室组织合作制定和实施通用标准，以及与美国食品药品监督管理局共同制定监管科学文件，来弥合生物标志物发现与鉴定之间的差距，以便向蛋白质组学界传授多重检测的分析评估要求，从而确保这些检测在预期用途中的安全性和有效性。
