Speer Runa, Wulfkuhle Julia, Espina Virginia, Aurajo Robyn, Edmiston Kirsten H, Liotta Lance A, Petricoin Emanuel F
University of Tubingen, Faculty of Medicine, Department of Obstetrics and Gynecology, Calwer Str. 7, 72076 Tubingen, Germany, and Department of Surgery, Inova Fairfax Hospital Cancer Center, Falls Church, VA, USA.
Cancer Genomics Proteomics. 2007 May-Jun;4(3):157-64.
While genomics provide important information about the somatic genetic changes, and RNA transcript profiling can reveal important expression changes that correlate with outcome and response to therapy, it is the proteins that do the work in the cell. At a functional level, derangements within the proteome, driven by post-translational and epigenetic modifications, such as phosphorylation, is the cause of a vast majority of human diseases. Cancer, for instance, is a manifestation of deranged cellular protein molecular networks and cell signaling pathways that are based on genetic changes at the DNA level. Importantly, the protein pathways contain the drug targets in signaling networks that govern overall cellular survival, proliferation, invasion and cell death. Consequently, the promise of proteomics resides in the ability to extend analysis beyond correlation to causality. A critical gap in the information knowledge base of molecular profiling is an understanding of the ongoing activity of protein signaling in human tissue: what is activated and "in use" within the human body at any given point in time. To address this gap, we have invented a new technology, called reverse phase protein microarrays, that can generate a functional read-out of cell signaling networks or pathways for an individual patient obtained directly from a biopsy specimen. This "wiring diagram" can serve as the basis for both, selection of a therapy and patient stratification.
虽然基因组学提供了有关体细胞遗传变化的重要信息，RNA转录谱分析可以揭示与疾病转归及治疗反应相关的重要表达变化，但细胞内发挥作用的是蛋白质。在功能层面上，由翻译后修饰和表观遗传修饰（如磷酸化）驱动的蛋白质组紊乱是绝大多数人类疾病的病因。例如，癌症是基于DNA水平的基因变化而导致的细胞蛋白质分子网络和细胞信号通路紊乱的一种表现。重要的是，蛋白质信号通路包含了调控细胞整体存活、增殖、侵袭和细胞死亡的信号网络中的药物靶点。因此，蛋白质组学的前景在于能够将分析从相关性扩展到因果关系。分子谱分析信息知识库中的一个关键空白是对人体组织中蛋白质信号传导的持续活性缺乏了解：即在任何给定时间点，人体内哪些信号被激活并正在“发挥作用”。为了填补这一空白，我们发明了一种新技术，称为反相蛋白质微阵列，它可以直接从活检标本中为个体患者生成细胞信号网络或信号通路的功能读数。这种“线路图”可作为治疗选择和患者分层的基础。
