Gulmann C, Sheehan K M, Kay E W, Liotta L A, Petricoin E F
NCI-FDA Clinical Proteomics Program, Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA.
J Pathol. 2006 Apr;208(5):595-606. doi: 10.1002/path.1958.
The human proteome, due to the enormity of post-translational permutations that result in large numbers of isoforms, is much more complex than the genome and alterations in cancer can occur in ways that are not predictable by translational analysis alone. Proteomic analysis therefore represents a more direct way of investigating disease at the individual patient level. Furthermore, since most novel therapeutic targets are proteins, proteomic analysis potentially has a central role in patient care. At the same time, it is becoming clear that mapping entire networks rather than individual markers may be necessary for robust diagnostics as well as tailoring of therapy. Consequently, there is a need for high-throughput multiplexed proteomic techniques, with the capability of scanning multiple cases and analysing large numbers of endpoints. New types of protein arrays combined with advanced bioinformatics are currently being used to identify molecular signatures of individual tumours based on protein pathways and signalling cascades. It is envisaged that analysing the cellular 'circuitry' of ongoing molecular networks will become a powerful clinical tool in patient management.
由于翻译后修饰排列的巨大差异会导致大量的蛋白质异构体，人类蛋白质组比基因组要复杂得多，癌症中的改变可能以仅靠转录分析无法预测的方式发生。因此，蛋白质组学分析是在个体患者层面研究疾病的更直接方法。此外，由于大多数新型治疗靶点是蛋白质，蛋白质组学分析在患者护理中可能具有核心作用。与此同时，越来越明显的是，绘制整个网络而非单个标志物对于可靠的诊断以及治疗方案的定制可能是必要的。因此，需要高通量多重蛋白质组学技术，具备扫描多个病例并分析大量终点的能力。新型蛋白质阵列与先进的生物信息学相结合，目前正被用于基于蛋白质途径和信号级联反应来识别个体肿瘤的分子特征。预计分析正在进行的分子网络的细胞“线路”将成为患者管理中一种强大的临床工具。
