Routine measurement of cancer biomarkers is performed for early detection, risk classification, and treatment monitoring, among other applications, and has substantially contributed to better clinical outcomes for patients. However, there remains an unmet need for clinically validated assays of cancer protein biomarkers. Protein tumor markers are of particular interest since proteins carry out the majority of biological processes and thus dynamically reflect changes in cancer pathophysiology. Mass spectrometry-based targeted proteomics is a powerful tool for absolute peptide and protein quantification in biological matrices with numerous advantages that make it attractive for clinical applications in oncology. The use of liquid chromatography-tandem mass spectrometry (LC–MS/MS) based methodologies has allowed laboratories to overcome challenges associated with immunoassays that are more widely used for tumor marker measurements. Yet, clinical implementation of targeted proteomics methodologies has so far been limited to a few cancer markers. This is due to numerous challenges associated with paucity of robust validation studies of new biomarkers and the labor-intensive and operationally complex nature of LC–MS/MS workflows. The purpose of this review is to provide an overview of targeted proteomics applications in cancer, workflows used in targeted proteomics, and requirements for clinical validation and implementation of targeted proteomics assays. We will also discuss advantages and challenges of targeted MS-based proteomics assays for clinical cancer biomarker analysis and highlight some recent developments that will positively contribute to the implementation of this technique into clinical laboratories.

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基于质谱的临床癌症生物标志物靶向蛋白质组学的最新进展

癌症生物标志物的常规测量用于早期检测、风险分类和治疗监测等应用，并且大大有助于改善患者的临床结果。然而，对癌症蛋白生物标志物的临床验证测定的需求仍然未得到满足。蛋白质肿瘤标志物特别令人感兴趣，因为蛋白质执行大部分生物过程，从而动态反映癌症病理生理学的变化。基于质谱的靶向蛋白质组学是生物基质中肽和蛋白质绝对定量的强大工具，具有众多优点，使其对肿瘤学的临床应用具有吸引力。使用基于液相色谱-串联质谱 (LC-MS/MS) 的方法使实验室能够克服与更广泛用于肿瘤标志物测量的免疫测定相关的挑战。然而，迄今为止，靶向蛋白质组学方法的临床实施仅限于少数癌症标志物。这是由于缺乏对新生物标记物的可靠验证研究以及 LC-MS/MS 工作流程的劳动密集型和操作复杂性所带来的众多挑战。本综述的目的是概述靶向蛋白质组学在癌症中的应用、靶向蛋白质组学中使用的工作流程以及临床验证和实施靶向蛋白质组学检测的要求。我们还将讨论用于临床癌症生物标志物分析的基于 MS 的靶向蛋白质组学测定的优势和挑战，并重点介绍一些将积极促进该技术在临床实验室中实施的最新进展。