Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, Australia; Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Queensland University of Technology, Brisbane, Australia.
Proteomics Clin Appl. 2014 Jun;8(5-6):403-15. doi: 10.1002/prca.201300098. Epub 2014 May 11.
Rapidly developing proteomic tools are improving detection of deregulated kallikrein-related peptidase (KLK) expression, at the protein level, in prostate and ovarian cancer, as well as facilitating the determination of functional consequences downstream. MS-driven proteomics uniquely allows for the detection, identification, and quantification of thousands of proteins in a complex protein pool, and this has served to identify certain KLKs as biomarkers for these diseases. In this review, we describe applications of this technology in KLK biomarker discovery and elucidate MS-based techniques that have been used for unbiased, global screening of KLK substrates within complex protein pools. Although MS-based KLK degradomic studies are limited to date, they helped to discover an array of novel KLK substrates. Substrates identified by MS-based degradomics are reported with improved confidence over those determined by incubating a purified or recombinant substrate and protease of interest, in vitro. We propose that these novel proteomic approaches represent the way forward for KLK research, in order to correlate proteolysis of biological substrates with tissue-related consequences, toward clinical targeting of KLK expression and function for cancer diagnosis, prognosis, and therapies.
快速发展的蛋白质组学工具正在提高对前列腺癌和卵巢癌中失调激肽释放酶相关肽酶（KLK）表达的检测，在蛋白质水平上，以及促进下游功能后果的确定。MS 驱动的蛋白质组学独特地允许在复杂的蛋白质池中检测、鉴定和定量数千种蛋白质，这有助于确定某些 KLK 作为这些疾病的生物标志物。在这篇综述中，我们描述了该技术在 KLK 生物标志物发现中的应用，并阐明了用于在复杂蛋白质池中进行 KLK 底物无偏、全局筛选的基于 MS 的技术。尽管基于 MS 的 KLK 降解组学研究目前受到限制，但它们有助于发现一系列新的 KLK 底物。通过 MS 基于降解组学鉴定的底物的报告置信度高于通过体外孵育纯化或重组底物和感兴趣的蛋白酶确定的那些。我们提出，这些新的蛋白质组学方法代表了 KLK 研究的前进方向，以便将生物底物的蛋白水解与组织相关的后果相关联，从而针对癌症诊断、预后和治疗进行 KLK 表达和功能的临床靶向。
