Mosaiques-Diagnostics GmbH, Hannover, Germany.
University Hospital RWTH Aachen, Institute for Molecular Cardiovascular Research (IMCAR), Aachen, Germany.
Mass Spectrom Rev. 2019 Jan;38(1):49-78. doi: 10.1002/mas.21572. Epub 2018 Jun 11.
Cancer is a heterogeneous multifactorial disease, which continues to be one of the main causes of death worldwide. Despite the extensive efforts for establishing accurate diagnostic assays and efficient therapeutic schemes, disease prevalence is on the rise, in part, however, also due to improved early detection. For years, studies were focused on genomics and transcriptomics, aiming at the discovery of new tests with diagnostic or prognostic potential. However, cancer phenotypic characteristics seem most likely to be a direct reflection of changes in protein metabolism and function, which are also the targets of most drugs. Investigations at the protein level are therefore advantageous particularly in the case of in-depth characterization of tumor progression and invasiveness. Innovative high-throughput proteomic technologies are available to accurately evaluate cancer formation and progression and to investigate the functional role of key proteins in cancer. Employing these new highly sensitive proteomic technologies, cancer biomarkers may be detectable that contribute to diagnosis and guide curative treatment when still possible. In this review, the recent advances in proteomic biomarker research in cancer are outlined, with special emphasis placed on the identification of diagnostic and prognostic biomarkers for solid tumors. In view of the increasing number of screening programs and clinical trials investigating new treatment options, we discuss the molecular connections of the biomarkers as well as their potential as clinically useful tools for diagnosis, risk stratification and therapy monitoring of solid tumors.
癌症是一种异质性的多因素疾病，仍然是全球主要死亡原因之一。尽管为建立准确的诊断检测和有效的治疗方案做出了广泛的努力，但疾病的流行率仍在上升，部分原因是早期检测的改善。多年来，研究集中在基因组学和转录组学上，旨在发现具有诊断或预后潜力的新检测方法。然而，癌症表型特征似乎最有可能直接反映蛋白质代谢和功能的变化，而这些也是大多数药物的靶点。因此，在蛋白质水平上进行研究特别有利于深入研究肿瘤的进展和侵袭性。创新的高通量蛋白质组学技术可用于准确评估癌症的形成和进展，并研究癌症中关键蛋白质的功能作用。采用这些新的高灵敏度蛋白质组学技术，可以检测到有助于诊断的癌症生物标志物，并在可能的情况下指导治疗。在这篇综述中，概述了癌症蛋白质组学生物标志物研究的最新进展，特别强调了用于诊断和预后的固体肿瘤生物标志物的鉴定。鉴于越来越多的筛查计划和临床试验正在研究新的治疗选择，我们讨论了生物标志物的分子联系及其作为固体肿瘤诊断、风险分层和治疗监测的临床有用工具的潜力。
