Gogalic S, Sauer U, Doppler S, Preininger C
Health & Environment Department, AIT Austrian Institute of Technology, Bioresources, Konrad Lorenz Straße 24, 3430 Tulln, Austria.
Analyst. 2015 Feb 7;140(3):724-35. doi: 10.1039/c4an01432d.
Bladder cancer (BCa) is a serious malignancy of the urinary tract worldwide and also prominent for its high rate of recurrence incorporating 50% of all treated patients. To reduce relapse of BCa, lifelong surveillance of patients is essential leading to high treatment costs. The gold standard for the diagnosis of bladder cancer is cystoscopy. It is very sensitive, but due to high costs and its invasive nature this method for routine diagnosis of bladder cancer remains questionable. Because of this and the required surveillance of patients suffering from bladder cancer, urine based markers represent a new potential field of investigation. Literature at the National Center of Biological Information (NCBI) was retrieved for a potential marker panel offering specific protein signatures and used to develop a sensitive and accurate chip assay to monitor BCa. Discovery of possible bladder cancer protein markers is compiled by extensive literature search including 1077 recently (15.01.2008-20.03.2014) published research articles. Validation of this literature is done by selection based on prior defined inclusion and exclusion criteria. A set of six putative biomarkers (VEGF, IL-8, MMP-9, MMP-7, survivin and Cyfra 21.1) was identified and a non-invasive microarray developed to be used for further clinical validation. Investigation regarding optimized urine preparation and assay development, to enhance assay sensitivity for the marker panel, was carried out. This protein based BCa chip enables the fast (within 5 h), simultaneous, easy to operate, cheap, early and non-invasive determination of BCa and is ready for clinical evaluation.
膀胱癌(BCa)是全球范围内一种严重的泌尿系统恶性肿瘤,其高复发率也很突出,所有接受治疗的患者中有50%会复发。为了降低膀胱癌的复发率,对患者进行终身监测至关重要,这导致了高昂的治疗成本。膀胱癌诊断的金标准是膀胱镜检查。它非常敏感,但由于成本高且具有侵入性,这种用于膀胱癌常规诊断的方法仍存在疑问。由于这一点以及对膀胱癌患者进行监测的必要性,基于尿液的标志物代表了一个新的潜在研究领域。在国家生物信息中心(NCBI)检索文献,寻找提供特定蛋白质特征的潜在标志物组合,并用于开发一种灵敏且准确的芯片检测方法来监测膀胱癌。通过广泛的文献检索(包括1077篇最近(2008年1月15日至2014年3月20日)发表的研究文章)来汇总可能的膀胱癌蛋白质标志物。根据预先确定的纳入和排除标准进行选择,对这些文献进行验证。确定了一组六个假定的生物标志物(血管内皮生长因子、白细胞介素-8、基质金属蛋白酶-9、基质金属蛋白酶-7、生存素和细胞角蛋白19片段),并开发了一种非侵入性微阵列用于进一步的临床验证。开展了关于优化尿液制备和检测方法开发的研究,以提高检测方法对标志物组合的敏感性。这种基于蛋白质的膀胱癌芯片能够快速(5小时内)、同时、易于操作、廉价、早期且非侵入性地检测膀胱癌,并且已准备好进行临床评估。