尿液蛋白质组作为下一代生物标志物的潜力

Urine is the Next-Generation Biomarker Source

生物标志物是与机体生理及病理生理状态相关的可监测到变化的生化指标,尿液不属于内环境,没有稳态机制,能够积累并反映机体生理状态的早期变化,有潜力辅助疾病的早期诊断和预后监测。得益于非侵入性的收集方式,尿液可以被连续、大量、重复收集并便捷、稳定地保存,且组分相对简单,易于分析,是理想的标志物研究样本。但临床尿液样本蛋白质组可能会受到生活习惯、用药情况等多种混杂因素的影响,而动物模型方便控制变量,可以最大程度减少混杂因素的干扰,并使得在疾病发生、发展极早期采集样本成为可能;此外,患者的疾病分期、分型、用药情况等信息不能被忽视,现有样本策略和分析方式有待优化,例如,对同一个人不同时期、不同状态(例如患病前后)的尿液样本进行前后对照是一种理想的分析方式,这种方式能够消除个体间差异性的影响,符合个性化、精准化医疗的趋势;在无自身对照样本的情况下,一对多的分析方法能够更好地体现个体与健康群体的差别,辅助未知疾病的诊断和鉴别。尿液大分子的膜保存方式使得临床样本的保存更加简单经济。尿液生物标志物领域研究的进步需要政策和伦理的支持、资金和人力长期持续的投入以及大样本、大数据的辅助。本文综述了尿液生物标志物的重要概念、理论思想、发展历程、研究现状、主要方法和技术以及未来展望等内容,期望能较为全面地展示尿液蛋白质组在生物标志物领域广阔的应用前景。

A biomarker is a measurable change associated with the biological process(including continuously from the healthy stage to the disease stage). According to the theory of homeostasis, urine accumulates all kinds of early changes of the body, so we can find subtle changes at the very beginning of the disease development. As urine is the better source of the next-generation biomarkers, urine biomarker studies are expected to greatly promote the development of medical technologies such as human disease diagnosis, prevention, treatment, or prognosis. However, the components found in clinical samples of urine are not only related to the disease, but also associated with many other confounding factors. Using animal models, we can eliminate interfering factors caused by medicine and other lifestyle factors and we can also study early biomarkers even before the earliest clinical symptoms appear. In biomarker studies of human samples, the effects of confounding factors such as therapeutic drugs must be considered. To discover small early changes in disease, pre-and-post control of the same person can minimize most interfering factors. The combined method of urine proteomics and one-to-many analysis can be applied to the exploration of any unknown disease. One-to-many analysis means a comparative analysis of one sample to many controls. In this way, changes in urinary proteins before, during and after disease and/or treatment can be found, which can provide useful information for early detection and evaluation of the disease condition and treatment effect. To sum up, the recognition of urinary biomarkers will require the support of the policy and ethical principles, the cooperation of more doctors and patients and the participation of more foundations and companies. This review focuses on the concepts, theoretical ideas, research status, methods and technologies, and prospects of urine biomarkers and urine proteomics.