Am J Epidemiol. 2015 May 1;181(9):635-47. doi: 10.1093/aje/kwu462. Epub 2015 Mar 19.
Proteome analysis is increasingly being used in investigations elucidating the molecular basis of disease, identifying diagnostic and prognostic markers, and ultimately improving patient care. We appraised the current status of proteomic investigations using human samples, including the state of the art in proteomic technologies, from sample preparation to data evaluation approaches, as well as key epidemiologic, statistical, and translational issues. We systematically reviewed the most highly cited clinical proteomic studies published between January 2009 and March 2014 that included a minimum of 100 samples, as well as strategies that have been successfully implemented to enhance the translational relevance of proteomic investigations. Limited comparability between studies and lack of specification of biomarker context of use are frequently observed. Nevertheless, there are initial examples of successful biomarker discovery in cross-sectional studies followed by validation in high-risk longitudinal cohorts. Translational potential is currently hindered, as limitations in proteomic investigations are not accounted for. Interdisciplinary communication between proteomics experts, basic researchers, epidemiologists, and clinicians, an orchestrated assimilation of required resources, and a more systematic translational outlook for accumulation of evidence may augment the public health impact of proteomic investigations.
蛋白质组学分析越来越多地用于研究阐明疾病的分子基础,鉴定诊断和预后标志物,并最终改善患者的护理。我们评估了使用人类样本进行的蛋白质组学研究的现状,包括蛋白质组学技术的最新进展,从样品制备到数据评估方法,以及关键的流行病学、统计学和转化问题。我们系统地回顾了 2009 年 1 月至 2014 年 3 月间发表的、包含至少 100 个样本的最具影响力的临床蛋白质组学研究,并介绍了成功实施的增强蛋白质组学研究转化相关性的策略。研究之间的可比性有限,并且经常缺乏生物标志物使用情况的说明。尽管如此,在横断面研究中已经有了成功发现生物标志物的初步例子,随后在高危纵向队列中进行了验证。由于没有考虑蛋白质组学研究的局限性,因此目前其转化潜力受到阻碍。蛋白质组学专家、基础研究人员、流行病学家和临床医生之间的跨学科交流、所需资源的协调同化,以及更系统的转化观点来积累证据,可能会增加蛋白质组学研究对公共卫生的影响。