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代谢组学衍生的前列腺癌生物标志物:事实还是虚构?

Metabolomics-derived prostate cancer biomarkers: fact or fiction?

作者信息

Kumar Deepak, Gupta Ashish, Mandhani Anil, Sankhwar Satya Narain

机构信息

Centre of Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences Campus , Raebareli Road, Lucknow, Uttar Pradesh 226 014, India.

出版信息

J Proteome Res. 2015 Mar 6;14(3):1455-64. doi: 10.1021/pr5011108. Epub 2015 Jan 29.

Abstract

Despite continuing research for precise probing and grading of prostate cancer (PC) biomarkers, the indexes lack sensitivity and specificity. To search for PC biomarkers, we used proton nuclear magnetic resonance ((1)H NMR)-derived serum metabolomics. The study comprises 102 serum samples obtained from low-grade (LG, n = 40) and high-grade (HG, n = 30) PC cases and healthy controls (HC, n = 32). (1)H NMR-derived serum data were examined using principal component analysis and orthogonal partial least-squares discriminant analysis. The strength of the model was verified by internal cross-validation using the same samples divided into 70% as training and 30% as test data sets. Receiver operating characteristic (ROC) curve examination was also achieved. Serum metabolomics reveals that four biomarkers (alanine, pyruvate, glycine, and sarcosine) were able to accurately (ROC 0.966) differentiate 90.2% of PC cases with 84.4% sensitivity and 92.9% specificity compared with HC. Similarly, three biomarkers, alanine, pyruvate, and glycine, were able to precisely (ROC 0.978) discriminate 92.9% of LG from HG PC with 92.5% sensitivity and 93.3% specificity. The robustness of these biomarkers was confirmed by prediction of the test data set with >99% diagnostic precision for PC determination. These findings demonstrate that (1)H NMR-based serum metabolomics is a promising approach for probing and grading PC.

摘要

尽管对前列腺癌(PC)生物标志物进行精确探测和分级的研究仍在继续,但这些指标缺乏敏感性和特异性。为了寻找PC生物标志物,我们使用了基于质子核磁共振((1)H NMR)的血清代谢组学。该研究包括从低级别(LG,n = 40)和高级别(HG,n = 30)PC病例以及健康对照(HC,n = 32)中获得的102份血清样本。使用主成分分析和正交偏最小二乘判别分析对基于(1)H NMR的血清数据进行了检查。通过内部交叉验证,将相同样本分为70%作为训练数据集和30%作为测试数据集,验证了模型的强度。还进行了受试者工作特征(ROC)曲线分析。血清代谢组学显示,四种生物标志物(丙氨酸、丙酮酸、甘氨酸和肌氨酸)能够准确地(ROC 0.966)区分90.2%的PC病例,与HC相比,敏感性为84.4%,特异性为92.9%。同样,三种生物标志物,丙氨酸、丙酮酸和甘氨酸,能够精确地(ROC 0.978)区分92.9%的LG和HG PC,敏感性为92.5%,特异性为93.3%。通过对测试数据集的预测,这些生物标志物在PC测定中的诊断精度>99%,从而证实了它们的稳健性。这些发现表明,基于(1)H NMR的血清代谢组学是一种用于探测和分级PC的有前景的方法。

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