Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore.
J Proteome Res. 2010 Jun 4;9(6):2988-95. doi: 10.1021/pr901173v.
Cystoscopy is considered the gold standard for the clinical diagnosis of human bladder cancer (BC). As cystoscopy is expensive and invasive, it may compromise patients' compliance and account for the failure in detecting recurrent BC in some patients. In this paper, we investigated the role of urinary metabonomics in the diagnosis of human BC. Gas chromatography/time-of-flight mass spectrometry was applied for the urinary metabolic profiling of 24 BC patients and 51 non-BC controls. The acquired data were analyzed using multivariate principal component analysis followed by orthogonal partial least-squares discriminant analysis (OPLS-DA). Model validity was verified using permutation tests and receiver operating characteristic (ROC) analysis. BC patients were clearly distinguished from non-BC subjects based on their global urinary metabolic profiles (OPLS-DA, 4 latent variables, R(2)X = 0.420, R(2)Y = 0.912 and Q(2) (cumulative) = 0.245; ROC AUC of 0.90; 15 marker metabolites). One-hundred percent sensitivity in detecting BC was observed using urinary metabonomics versus 33% sensitivity achieved by urinary cytology. Additionally, urinary metabonomics exhibited potential in the staging and grading of bladder tumors. In summary, urinary metabonomics is amenable for the noninvasive diagnosis of human BC.
膀胱镜检查被认为是人类膀胱癌 (BC) 临床诊断的金标准。由于膀胱镜检查既昂贵又具有侵入性，可能会影响患者的依从性，并导致一些患者复发的 BC 无法被检测到。在本文中，我们研究了尿代谢组学在人类 BC 诊断中的作用。应用气相色谱/飞行时间质谱对 24 名 BC 患者和 51 名非 BC 对照者的尿液代谢谱进行了分析。采用多元主成分分析结合正交偏最小二乘判别分析 (OPLS-DA) 对所获得的数据进行了分析。采用置换检验和接收者操作特征 (ROC) 分析验证了模型的有效性。根据全局尿液代谢谱 (OPLS-DA，4 个潜在变量，R(2)X = 0.420，R(2)Y = 0.912 和 Q(2)(累积) = 0.245；ROC AUC 为 0.90；15 种标记代谢物)，BC 患者与非 BC 患者明显区分开来。与尿液细胞学 33%的灵敏度相比，尿液代谢组学检测 BC 的灵敏度达到 100%。此外，尿液代谢组学在膀胱肿瘤的分期和分级中具有潜在的应用价值。总之，尿液代谢组学适用于人类 BC 的非侵入性诊断。
