Manchester Academic Health Science Centre, University of Manchester, UK.
Arch Toxicol. 2011 Jan;85(1):5-17. doi: 10.1007/s00204-010-0609-6. Epub 2010 Oct 16.
Metabolomics allows the simultaneous and relative quantification of thousands of different metabolites within a given sample using sensitive and specific methodologies such as gas or liquid chromatography coupled to mass spectrometry, typically in discovery phases of studies. Biomarkers are biological characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathological processes or pharmacologic responses to a therapeutic intervention. Biomarkers are widely used in clinical practice for the diagnosis, assessment of severity and response to therapy in a number of clinical disease states. In human studies, metabolomics has been applied to define biomarkers related to prognosis or diagnosis of a disease or drug toxicity/efficacy and in doing so hopes to provide greater pathophysiological understanding of disease or therapeutic toxicity/efficacy. This review discusses the application of metabolomics in the discovery and subsequent application of biomarkers in the diagnosis and management of inborn errors of metabolism, cardiovascular disease and cancer. We critically appraise how novel biomarkers discovered through metabolomic analysis may be utilized in future clinical practice by addressing the following three fundamental questions: (1) Can the clinician measure them? (2) Do they add new information? (3) Do they help the clinician to manage patients? Although a number of novel biomarkers have been discovered through metabolomic studies of human diseases in the last decade, none have currently made the transition to routine use in clinical practice. Metabolites identified from these early studies will need to form the basis of larger, prospective, externally validated studies in clinical cohorts for their future use as biomarkers. At this stage, the absolute quantification of these biomarkers will need to be assessed epidemiologically, as will the ultimate deployment in the clinic via routine biochemistry, dip stick or similar rapid at- or near-patient care technologies.
代谢组学允许使用敏感和特异的方法学（如气相或液相色谱与质谱联用）同时且相对定量给定样本中的数千种不同代谢物，通常在研究的发现阶段。生物标志物是客观测量和评估的生物学特征，作为正常生物学过程、病理过程或药物治疗反应的指标。生物标志物广泛应用于临床实践中，用于诊断、评估许多临床疾病状态下的严重程度和对治疗的反应。在人类研究中，代谢组学已被用于定义与疾病的预后或诊断、药物毒性/疗效相关的生物标志物，并希望借此提供对疾病或治疗毒性/疗效的更大病理生理学理解。本综述讨论了代谢组学在发现生物标志物及其随后在诊断和管理先天性代谢错误、心血管疾病和癌症中的应用。我们通过解决以下三个基本问题来批判性地评估通过代谢组学分析发现的新型生物标志物在未来临床实践中的应用潜力：（1）临床医生能否测量它们？（2）它们是否提供新信息？（3）它们是否有助于临床医生管理患者？尽管在过去十年中，通过对人类疾病的代谢组学研究已经发现了许多新型生物标志物，但目前没有一种已经过渡到常规临床实践中使用。这些早期研究中鉴定的代谢物将需要作为基础，在临床队列中进行更大规模的、前瞻性的、外部验证的研究，以用于未来作为生物标志物。在现阶段，这些生物标志物的绝对定量需要通过流行病学进行评估，并且需要通过常规生化、试条或类似的快速床边护理技术在临床上最终部署。
