Quantitative label-free proteomic analysis of human urine to identify novel candidate protein biomarkers for schistosomiasis

Background
Schistosomiasis is a chronic neglected tropical disease that is characterized by continued inflammatory challenges to the exposed population and it has been established as a possible risk factor in the aetiology of bladder cancer. Improved diagnosis of schistosomiasis and its associated pathology is possible through mass spectrometry to identify biomarkers among the infected population, which will influence early detection of the disease and its subtle morbidity.
Methodology
A high-throughput proteomic approach was used to analyse human urine samples for 49 volunteers from Eggua, a schistosomiasis endemic community in South-West, Nigeria. The individuals were previously screened for Schistosoma haematobium and structural bladder pathologies via microscopy and ultrasonography respectively. Samples were categorised into schistosomiasis, schistosomiasis with bladder pathology, bladder pathology, and a normal healthy control group. These samples were analysed to identify potential protein biomarkers.
Results
A total of 1306 proteins and 9701 unique peptides were observed in this study (FDR = 0.01). Fifty-four human proteins were found to be potential biomarkers for schistosomiasis and bladder pathologies due to schistosomiasis by label-free quantitative comparison between groups. Thirty-six (36) parasite-derived potential biomarkers were also identified, which include some existing putative schistosomiasis biomarkers that have been previously reported. Some of these proteins include Elongation factor 1 alpha, phosphopyruvate hydratase, histone H4 and heat shock proteins (HSP 60, HSP 70).
Conclusion
These findings provide an in-depth analysis of potential schistosoma and human host protein biomarkers for diagnosis of chronic schistosomiasis caused by Schistosoma haematobium and its pathogenesis.

Background
血吸虫病（Schistosomiasis）是一种慢性被忽视的热带病，以暴露人群持续遭受炎症刺激为特征，现已被证实是膀胱癌病因学中的潜在危险因素。通过质谱（mass spectrometry）技术在感染人群中筛选生物标志物，可实现血吸虫病及其相关病理的精准诊断，这将有助于该疾病的早期发现及其隐匿性病症的识别。
Methodology
本研究采用高通量蛋白质组学方法，对来自尼日利亚西南部血吸虫病流行社区埃瓜（Eggua）的49名志愿者的尿液样本开展分析。所有受试者此前分别通过显微镜检查与超声检查，筛查了埃及血吸虫（Schistosoma haematobium）感染及膀胱结构病变情况。研究将样本分为血吸虫感染组、血吸虫感染合并膀胱病变组、单纯膀胱病变组与正常健康对照组，并通过分析上述样本以筛选潜在的蛋白质生物标志物。
Results
本研究共检测到1306种蛋白质与9701条独特肽段（错误发现率FDR=0.01）。通过组间无标记定量比较，共筛选出54种与血吸虫病及血吸虫相关膀胱病变相关的人类宿主潜在生物标志物。此外还鉴定出36种寄生虫源性潜在生物标志物，其中包含部分既往已报道的推定血吸虫病生物标志物。上述蛋白质包括延伸因子1α（Elongation factor 1 alpha）、磷酸丙酮酸水合酶（phosphopyruvate hydratase）、组蛋白H4（histone H4）以及热休克蛋白（heat shock proteins，HSP 60、HSP 70）等。
Conclusion
本研究结果为埃及血吸虫所致慢性血吸虫病及其发病机制的诊断，提供了潜在的血吸虫源性与人类宿主源性蛋白质生物标志物的深度分析依据。