Larkin S E T, Johnston H E, Jackson T R, Jamieson D G, Roumeliotis T I, Mockridge C I, Michael A, Manousopoulou A, Papachristou E K, Brown M D, Clarke N W, Pandha H, Aukim-Hastie C L, Cragg M S, Garbis S D, Townsend P A
Cancer Sciences Unit, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK.
Institute of Cancer Sciences, Manchester Cancer Research Centre, Manchester Academic Health Science Centre, University of Manchester, Wilmslow Road, Manchester M20 4QL, UK.
Br J Cancer. 2016 Oct 25;115(9):1078-1086. doi: 10.1038/bjc.2016.291. Epub 2016 Sep 29.
Prostate cancer (PCa) is the most common male cancer in the United Kingdom and we aimed to identify clinically relevant biomarkers corresponding to stage progression of the disease.
We used enhanced proteomic profiling of PCa progression using iTRAQ 3D LC mass spectrometry on high-quality serum samples to identify biomarkers of PCa.
We identified >1000 proteins. Following specific inclusion/exclusion criteria we targeted seven proteins of which two were validated by ELISA and six potentially interacted forming an 'interactome' with only a single protein linking each marker. This network also includes accepted cancer markers, such as TNF, STAT3, NF-κB and IL6.
Our linked and interrelated biomarker network highlights the potential utility of six of our seven markers as a panel for diagnosing PCa and, critically, in determining the stage of the disease. Our validation analysis of the MS-identified proteins found that SAA alongside KLK3 may improve categorisation of PCa than by KLK3 alone, and that TSR1, although not significant in this model, might also be a clinically relevant biomarker.
前列腺癌（PCa）是英国最常见的男性癌症，我们旨在确定与该疾病分期进展相对应的临床相关生物标志物。
我们使用iTRAQ 3D液相色谱质谱联用技术对高质量血清样本进行前列腺癌进展的增强蛋白质组分析，以鉴定前列腺癌的生物标志物。
我们鉴定出1000多种蛋白质。遵循特定的纳入/排除标准，我们针对7种蛋白质，其中2种通过酶联免疫吸附测定（ELISA）得到验证，6种可能相互作用形成一个“相互作用组”，每种标志物仅由一种蛋白质相连。该网络还包括公认的癌症标志物，如肿瘤坏死因子（TNF）、信号转导和转录激活因子3（STAT3）、核因子κB（NF-κB）和白细胞介素6（IL6）。
我们的相互关联的生物标志物网络突出了我们7种标志物中的6种作为诊断前列腺癌以及至关重要的确定疾病分期的一组标志物的潜在效用。我们对质谱鉴定的蛋白质的验证分析发现，血清淀粉样蛋白A（SAA）与激肽释放酶3（KLK3）一起使用可能比单独使用KLK3能更好地对前列腺癌进行分类，并且，尽管在该模型中无显著意义，但睾丸特异性丝氨酸蛋白酶抑制剂1（TSR1）也可能是一种临床相关生物标志物。
