Department of Medicine, Division of Nephrology, University of Toronto, Toronto, Ontario, Canada.
Clin Chem. 2012 Feb;58(2):353-65. doi: 10.1373/clinchem.2011.165969. Epub 2011 Oct 6.
Technological advances have resulted in a renaissance of proteomic studies directed at finding markers of disease progression, diagnosis, or responsiveness to therapy. Renal diseases are ideally suited for such research, given that urine is an easily accessible biofluid and its protein content is derived mainly from the kidney. Current renal prognostic markers have limited value, and renal biopsy remains the sole method for establishing a diagnosis. Mass spectrometry instruments, which can detect thousands of proteins at nanomolar (or even femtomolar) concentrations, may be expected to allow the discovery of improved markers of progression, diagnosis, or treatment responsiveness.
In this review we describe the strengths and limitations of proteomic methods and the drawbacks of existing biomarkers, and provide an overview of opportunities in the field. We also highlight several proteomic studies of biomarkers of renal diseases selected from the plethora of studies performed.
It is clear that the field of proteomics has not yet fulfilled its promise. However, ongoing efforts to standardize sample collection and preparation, improve study designs, perform multicenter validations, and create joint industry-regulatory bodies offer promise for the recognition of novel molecules that could change clinical nephrology forever.
技术进步使得针对疾病进展、诊断或治疗反应的标志物的蛋白质组学研究重新兴起。鉴于尿液是一种易于获取的生物流体,并且其蛋白质含量主要来自肾脏,因此肾脏疾病非常适合此类研究。目前的肾脏预后标志物的价值有限,肾脏活检仍然是确定诊断的唯一方法。质谱仪器可以在纳摩尔(甚至飞摩尔)浓度下检测数千种蛋白质,有望发现改进的疾病进展、诊断或治疗反应标志物。
在这篇综述中,我们描述了蛋白质组学方法的优缺点和现有生物标志物的缺点,并概述了该领域的机会。我们还从众多已完成的研究中选择了几个肾脏疾病生物标志物的蛋白质组学研究进行了重点介绍。
很明显,蛋白质组学领域尚未实现其承诺。然而,正在努力标准化样本采集和准备、改进研究设计、进行多中心验证以及创建联合行业监管机构,这为识别可能永远改变临床肾脏病学的新分子提供了希望。