Assessment of high-throughput high-resolution MALDI-TOF-MS of urinary peptides for the detection of muscle-invasive bladder cancer
Assessment of high-throughput high-resolution MALDI-TOF-MS of urinary peptides for the detection of muscle-invasive bladder cancer
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DOI：
10.1002/prca.201100011
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发表时间：
2011-10-01
影响因子：
2
通讯作者：
Ward, Douglas G.
中科院分区：
文献类型：
--
作者：
Bryan, Richard T.;Wei, Wenbin;Ward, Douglas G.
目的：需要更好的生物标志物来检测膀胱癌，并区分肌肉侵袭性（T2+期）和非侵袭性（Ta/T1期）疾病。我们评估MALDI-TOF-MS是否可以实现这一目标。实验设计：我们分析了751例膀胱癌患者和127例非膀胱癌患者的尿液。内源性肽谱分析使用Bruker Ultraflextreme MALDI-TOF-MS进行。结果：T2+病变患者与非T2+病变患者的尿谱有显著差异。T2+患者白蛋白、总蛋白和血尿均升高。39%的Ta/T1疾病患者和77%的T2+疾病患者检测到血尿。基于MALDI数据的类别预测模型在接收者-操作者特征曲线下产生的面积高达0.76，但没有明显优于单独基于总蛋白的模型。许多与侵袭性疾病显著相关的肽是丰富的血蛋白片段，也与血尿相关。结论及临床意义：显微镜下血尿与侵袭性疾病密切相关；即使是血液/血浆的痕迹也会强烈影响尿肽酶。当使用“组学”方法搜索尿液生物标志物时，需要考虑到这一点，因为血液蛋白可能会产生假阳性结果。
Purpose: There is a need for better biomarkers to both detect bladder cancer and distinguish muscle-invasive (stage T2+) from non-invasive (stage Ta/T1) disease. We assess whether MALDI-TOF-MS of the urine peptidome can achieve this.Experimental design: We analysed urine from 751 patients with bladder cancer and 127 patients without bladder cancer. Endogenous peptide profiling was performed using a Bruker Ultraflextreme MALDI-TOF-MS.Results: Significant differences were seen between the spectra of urine from patients with and without T2+ disease. Albumin, total protein and haematuria were also elevated in T2+ patients. Haematuria was detected in 39% of patients with Ta/T1 disease and in 77% of patients with T2+ disease. Class prediction models based on MALDI data produced areas under receiver-operator characteristic curves of up to 0.76 but did not significantly outperform a model based on total protein alone. Many peptides significantly associated with invasive disease are fragments of abundant blood proteins and are also associated with haematuria.Conclusions and clinical relevance: Microscopic haematuria is strongly associated with invasive disease; even traces of blood/plasma strongly influence the urinary peptidome. This needs to be taken into consideration when using 'omic' methods to search for urinary biomarkers as blood proteins may give false-positive results.