Cancer biomarkers have transformed current practices in the oncology clinic. Continued discovery and validation are crucial for improving early diagnosis, risk stratification, and monitoring patient response to treatment. Profiling of the tumour genome and transcriptome are now established tools for the discovery of novel biomarkers, but alterations in proteome expression are more likely to reflect changes in tumour pathophysiology. In the past, clinical diagnostics have strongly relied on antibody-based detection strategies, but these methods carry certain limitations. Mass spectrometry (MS) is a powerful method that enables increasingly comprehensive insights into changes of the proteome to advance personalized medicine. In this review, recent improvements in MS-based clinical proteomics are highlighted with a focus on oncology. We will provide a detailed overview of clinically relevant samples types, as well as, consideration for sample preparation methods, protein quantitation strategies, MS configurations, and data analysis pipelines currently available to researchers. Critical consideration of each step is necessary to address the pressing clinical questions that advance cancer patient diagnosis and prognosis. While the majority of studies focus on the discovery of clinically-relevant biomarkers, there is a growing demand for rigorous biomarker validation. These studies focus on high-throughput targeted MS assays and multi-centre studies with standardized protocols. Additionally, improvements in MS sensitivity are opening the door to new classes of tumour-specific proteoforms including post-translational modifications and variants originating from genomic aberrations. Overlaying proteomic data to complement genomic and transcriptomic datasets forges the growing field of proteogenomics, which shows great potential to improve our understanding of cancer biology. Overall, these advancements not only solidify MS-based clinical proteomics’ integral position in cancer research, but also accelerate the shift towards becoming a regular component of routine analysis and clinical practice.

中文翻译：

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基于质谱的临床蛋白质组学的最新进展：在癌症研究中的应用。

癌症生物标志物改变了肿瘤临床的当前实践。持续的发现和验证对于改善早期诊断、风险分层和监测患者对治疗的反应至关重要。肿瘤基因组和转录组的分析现已成为发现新型生物标志物的既定工具，但蛋白质组表达的改变更有可能反映肿瘤病理生理学的变化。过去，临床诊断强烈依赖基于抗体的检测策略，但这些方法具有一定的局限性。质谱 (MS) 是一种强大的方法，可以更加全面地了解蛋白质组的变化，从而推进个性化医疗。在这篇综述中，重点介绍了基于 MS 的临床蛋白质组学的最新进展，重点关注肿瘤学。我们将提供临床相关样品类型的详细概述，以及对研究人员目前可用的样品制备方法、蛋白质定量策略、MS 配置和数据分析流程的考虑。为了解决促进癌症患者诊断和预后的紧迫临床问题，必须认真考虑每个步骤。虽然大多数研究侧重于临床相关生物标志物的发现，但对严格生物标志物验证的需求不断增长。这些研究侧重于高通量靶向 MS 检测和采用标准化方案的多中心研究。此外，MS 灵敏度的提高为新型肿瘤特异性蛋白质形式打开了大门，包括翻译后修饰和源自基因组畸变的变异。叠加蛋白质组数据来补充基因组和转录组数据集，形成了不断发展的蛋白质基因组学领域，这在提高我们对癌症生物学的理解方面显示出巨大的潜力。总体而言，这些进步不仅巩固了基于 MS 的临床蛋白质组学在癌症研究中的不可或缺的地位，而且加速了其成为常规分析和临床实践的常规组成部分的转变。